David Mundell has insisted their will be no talks with Nicola Sturgeon until after Brexit
The Scottish Secretary flatly rejected the prospect of negotiations over a second poll on separation while a post-Brexit relationship is forged with Brussels.
Prime Minister Theresa May has already blocked Ms Sturgeon preferred timescale asserting "now is not the time" even for discussions.
Mr Mundell's comments are the clearest signal yet the UK Government hopes to push any plebiscite back by at least five years.
He said quitting the EU in March 2019 may involve "transitional measures" and require "significant implementation time".
It came after MSPs formally backed Ms Sturgeon's call for the powers to hold a ballot on Scotland's future.
The Greens joined forced with the SNP to push through a controversial motion authorising her to seek a Section 30 order from Westminster to hold a legally binding poll.
Ms Sturgeon wants a re-run of the 2014 vote to take place between autumn 2018 and spring 2019.
She argues this is needed to allow voters to decide what path to follow in the wake last June's Brexit vote.
I hope the UK Government will respect the will of this parliament
First Minster Nicola Sturgeon
But Mrs May insisted she won't change her mind on rejecting another referendum following showdown talks with Ms Sturgeon in Glasgow on Monday.
The First Minister reopened the debate – stalled by last Wednesday's Westminster terror attack – insisting voters should be given a choice.
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With Mrs May set to trigger Article 50 and begin the formal process of leaving the EU tomorrow, Ms Sturgeon said she would delay making the official Section 30 request until "later this week".
LIVE: Scotland reacts as Sturgeon gets her referendum Tue, March 28, 2017
A total of 69 MSPs voted to hold another referendum and 59 voted against
AFP/Getty Images 1 of 11
Scotland's First Minister Nicola Sturgeon (R) reacts as she leaves the chamber following a vote on the second day of the 'Scotland's Choice' debate on a motion to seek the authority to hold an indpendence referendum at the Scottish Parliament in Edinburgh
The SNP leader aslo said she will reveal next month how she will respond if the UK Government continues to block her calls.
She insisted she did not want confrontation and claimed she only wanted "sensible discussions".
Ms Sturgeon added: "I hope the UK Government will respect the will of this parliament.
"If it does so, I will enter discussion in good faith and with a willingness to compromise.
"However, if it chooses not to do so I will return to the parliament following the Easter recess to set out the steps that the Scottish Government will take to progress the will of parliament."
But during heated clashes Tory leader Ruth Davidson branded her plans a "farce" and accused Ms Sturgeon of "cooking up the same old recipe for division".
Tory leader Ruth Davidson accused the SNP leader of 'cooking up the same old recipe for division'
She also mocked Ms Sturgeon over her claims that Prime Minister had told her the UK's exit terms and a free trade deal would be agreed by March 2019.
At one point she told the First Minister to "sit down" as she refused to let her intervene, hitting out Ms Sturgeon's "rushed timetable" for a referendum.
Conservative, Labour and Lib Dem MSPs all opposed Ms Sturgeon's call.
MSPs voted 69 to 59 in favour of a Government motion, amended by the pro-independence Greens, seeking a Section 30 order as well as giving EU citizens and 16 and 17 year olds a vote.
Speaking after the ballot Ms Sturgeon insisted the mandate for another poll was "beyond question" and added: "It is up to the UK Government to now make clear when they consider a referendum would be appropriate."
But Mr Mundell told BBC Scotland there would be no "negotiations at all until the Brexit process is complete".
He added: "We're not entering into negotiations on whether there should be another independence referendum during the Brexit process.
"We don't have a crystal ball as to how long that process will take. We don't recognise, for example, 18 months as being a key point in the journey.
"It will be a journey that will involve the negotiations with the EU, it may be a journey that involves transitional measures, it may be a journey that will involve significant implementation time.
Kezia Dugdale remained the First Minister that Scotland voted decisively to remain in the UK in 2014
"It’s not appropriate to have a referendum whilst people do not know what the future relationship between the UK and the EU is and they won’t know that until theBrexit process is complete.”
This means a poll would be unlikely to take place before 2022 because of the time taken to complete trade arrangements, planned elections, and the period needed to make referendum arrangements.
Ms Davidson said: "We will continue to oppose a second referendum every step of the way.
"The majority of people in Scotland do not want it and the SNP does not have a clear mandate to pursue it."
Scottish Labour leader Kezia Dugdale insisted Scotland had voted "decisively" to remain in the UK in the 2014 referendum, and warned the First Minister: "We are divided enough, do not divide us again."
Lib Dem leader Willie Rennie said: "Scottish Liberal Democrats stood on a manifesto to oppose a divisive referendum and we will continue to do that."