Triethylamine → [(S)-3-(4-Fluoro-benzyl)piperidin-1-yl]-[(3S,4R)-3-((R)-1-phenyl-ethylamino)-tetrahydro-pyran-4-yl]-methanone

HRID 1169239Notes

Reaction equation

HRID 1169239 reaction equation
[C:1]1([C@H:7]([NH:9][C@H:10]2[C@H:15]([C:16]([OH:18])=O)[CH2:14][CH2:13][O:12][CH2:11]2)[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:59][C:60]1[CH:72]=[CH:71][C:63]([CH2:64][C@@H:65]2[CH2:70][CH2:69][CH2:68][NH:67][CH2:66]2)=[CH:62][CH:61]=1>ClCCl>[F:59][C:60]1[CH:61]=[CH:62][C:63]([CH2:64][C@@H:65]2[CH2:70][CH2:69][CH2:68][N:67]([C:16]([C@@H:15]3[CH2:14][CH2:13][O:12][CH2:11][C@H:10]3[NH:9][C@@H:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH3:8])=[O:18])[CH2:66]2)=[CH:71][CH:72]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 12174831(S)-3-(4-Fluorobenzyl)piperidineHCID 59042160(3S,4R)-3-[(R)-1-Phenyl-ethylamino]-tetrahydro-pyran-4-carboxylic acid

Product 1

HCID 69748122[(S)-3-(4-Fluoro-benzyl)piperidin-1-yl]-[(3S,4R)-3-((R)-1-phenyl-ethylamino)-tetrahydro-pyran-4-yl]-methanoneYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A cloudy solution of (3S,4R)-3-[(R)-1-Phenyl-ethylamino]-tetrahydro-pyran-4-carboxylic acid (containing sodium chloride; 943 mg, 2.57 mmol) in dichloromethane (25 mL) was treated with benzotriazol-1-yloxy-tripyrrolidinophosphonium hexafluorophosphate (1.61 g, 3.09 mmol) and triethylamine (826 μL, 5.92 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 18 h , the mixture was washed with water and saturated NaHCO3, dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (75% ethyl acetate/hexanes) to provide the product as a gum (1.10 g, 100%). 1H NMR (300 mHz, CDCl3) δ7.4-7.3 (m, 5H), 7.12 (m, 2H), 6.99 (t, 2H), 4.55 (bd, 1H), 3.87 (m, 2H), 3.70 (m, 2H), 3.4-2.8 (m, 3H), 2.66 (m, 2H), 2.42 (m, 2H), 2.0-1.1 (m, 9H), 1.34 (d, J=6.6 Hz, 3H), ESI MS: (M+H)+=425.3.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature
  3. waitAfter 18 h
  4. washthe mixture was washed with water and saturated NaHCO3
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4034ddba0bfe4db697c79276189e0c3b
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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