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

HRID 497491Notes

Reaction equation

HRID 497491 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%).

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-26d0ae3fda434d5db39e21706aad84e9
Source dataset
uspto-grants-2005_09
Patent number
US06949546B2

Reaction notes

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