Triethylsilane → (3R,4S)-4-[(R)-1-phenyl-ethylamino]-tetrahydrothiophene-3-carboxylic acid methyl ester

HRID 497495Notes

Reaction equation

HRID 497495 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH2:6][S:7][CH2:8][C:9]=1[NH:10][C@@H:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:12])=[O:4].C([SiH](CC)CC)C>FC(F)(F)C(O)=O>[CH3:1][O:2][C:3]([C@H:5]1[C@H:9]([NH:10][C@@H:11]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH3:12])[CH2:8][S:7][CH2:6]1)=[O:4]

Participants

4

Reactant 2

HCID 12052Triethylsilane2×HCID 69749255(R)-4-(1-Phenyl-ethylamino)-2,5-dihydrothiophene-3-carboxylic acid methyl ester

Product 1

HCID 69750268(3R,4S)-4-[(R)-1-phenyl-ethylamino]-tetrahydrothiophene-3-carboxylic acid methyl esterYield 28%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of crude (R)-4-(1-Phenyl-ethylamino)-2,5-dihydrothiophene-3-carboxylic acid methyl ester (2.82 g, ca. 9.1 mmol) was dissolved in trifluoroacetic acid (50 mL) and treated with triethylsilane (4.4 mL, 27.4 mmol). The mixture was stirred for 20 h, when TLC indicated residual starting material. Additional triethylsilane (1.5 mL) was added and the mixture was heated at reflux for 3 h, then was cooled and concentrated. The residue was dissolved in water and adjusted to pH 10 with 50% sodium hydroxide. The mixture was extracted with ether, and the combined organic phases were dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (15-30% diethyl ether/petroleum ether) to provide the product as a colorless oil (673 mg, 28%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 3 h
  3. temperaturewas cooled
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in water
  6. extractionThe mixture was extracted with ether
  7. dry with materialthe combined organic phases were dried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography (15-30% diethyl ether/petroleum ether)

Sources & evidence

ORD record
ord-ed32c77fe7f645b1b668ac573a341d5c
Source dataset
uspto-grants-2005_09
Patent number
US06949546B2

Reaction notes

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