Triethylamine → [(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-[(3R,4S)-4-((R)-1-phenyl-ethylamino)-tetrahydrothiophen-3-yl]-methanone

HRID 497497Notes

Reaction equation

HRID 497497 reaction equation
[C:1]1([C@H:7]([NH:9][C@@H:10]2[CH2:14][S:13][CH2:12][C@H:11]2[C:15]([OH:17])=O)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(CC)CC)C.[F:58][C:59]1[CH:71]=[CH:70][C:62]([CH2:63][C@@H:64]2[CH2:69][CH2:68][CH2:67][NH:66][CH2:65]2)=[CH:61][CH:60]=1>ClCCl>[F:58][C:59]1[CH:60]=[CH:61][C:62]([CH2:63][C@@H:64]2[CH2:69][CH2:68][CH2:67][N:66]([C:15]([C@H:11]3[C@H:10]([NH:9][C@@H:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH3:8])[CH2:14][S:13][CH2:12]3)=[O:17])[CH2:65]2)=[CH:70][CH:71]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 12174831(S)-3-(4-Fluorobenzyl)piperidineHCID 69750189(3R,4S)-4-[(R)-1-phenyl-ethylamino]-tetrahydrothiophene-3-carboxylic acid

Product 1

HCID 69747757[(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-[(3R,4S)-4-((R)-1-phenyl-ethylamino)-tetrahydrothiophen-3-yl]-methanoneYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A cloudy solution of (3R,4S)-4-[(R)-1-phenyl-ethylamino]-tetrahydrothiophene-3-carboxylic acid (containing sodium chloride; 928 mg, 2.54 mmol) in dichloromethane (20 mL) was treated with benzotriazol-1-yloxy-tripyrrolidinophosphonium hexafluorophosphate (1.59 g, 3.05 mmol) and triethylamine (814 μL, 5.84 mmol) and stirred for 5 minutes. A solution of the (S)-3-(4-fluorobenzyl)-piperidine prepared above in dichloromethane (5 mL) was added and the mixture was stirred at room temperature. After 21.5 h, the mixture was diluted with dichloromethane, washed with water and saturated NaHCO3, dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (55% ethyl acetate/hexanes) to provide the product as a gum (1.05 g, 94%).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature
  3. waitAfter 21.5 h
  4. washwashed with water and saturated NaHCO3
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (55% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-583723ff548242e0924d43b4805f1efe
Source dataset
uspto-grants-2005_09
Patent number
US06949546B2

Reaction notes

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