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

HRID 1169246Notes

Reaction equation

HRID 1169246 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%). 1H NMR (300 mHz, CDCl3) δ7.32 (m, 4H), 7.27 (m, 1H), 7.10 (m, 2H), 6.99 (m, 2H), 4.47 (m, 1H), 3.9-3.6 (m, 3H), 3.2 (m, 1H), 2.95 (m, 2H), 2.8-2.4 (m, 6H), 1.9-1.6 (m, 4H), 1.4 (m, 1H), 1.37 (m, 3H), 1.2 (m, 1H), ESI MS: (M+H)+=427.4.

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-dbaee80b4ea7426682873c797c995d85
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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