Acetic Acid → (3S,4S)-3-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-4-[(R)-1-phenyl-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1169256Notes

Reaction equation

HRID 1169256 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([NH:13][C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[C@H:10]([C:22]([N:24]2[CH2:29][CH2:28][CH2:27][C@@H:26]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[CH2:25]2)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O1CCCC1.C(O)(=O)C>CO>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([NH:13][C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[C@@H:10]([CH2:22][N:24]2[CH2:29][CH2:28][CH2:27][C@@H:26]([CH2:30][C:31]3[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=3)[CH2:25]2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 69748530(3R,4S)-3-[(S)-3-(4-fluorobenzyl)-piperidine-1-carbonyl]-4-[(R)-1-phenyl-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 69748103(3S,4S)-3-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-4-[(R)-1-phenyl-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 68.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(3R,4S)-3-[(S)-3-(4-fluorobenzyl)-piperidine-1-carbonyl]-4-[(R)-1-phenyl-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (150 mg, 294 μmol) ) was treated with borane-tetrahydrofuran complex in tetrahydrofuran (1.0 M; 11.64 mL, 11.64 mmol) and stirred for 20 h . The mixture was treated slowly with 20% acetic acid in methanol (20 mL), and the resulting mixture was stirred at room temperature for 36 h . The solvents were removed, and the residue was dissolved in water, made basic (pH 11) with 50% sodium hydroxide, and extracted with dichloromethane. The combined organic phases were dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (60% ethyl acetate/hexane) to provide the product (100 mg, 68%). 1H NMR (300 mHz, CD3OD) δ7.31-7.00 (9H), 3.78 (m, 1H), 3.42 (m, 1H), 3.22-1.62 (18H), 1.39 (d, 3H), 1.34 (s, 9H); mass spec. (ES+) m/z 496.5.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 36 h
  2. customThe solvents were removed
  3. dissolutionthe residue was dissolved in water
  4. extractionextracted with dichloromethane
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9251d33dbe7448c0a90e968dce0ceda1
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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