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

HRID 1169255Notes

Reaction equation

HRID 1169255 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13]([N:15]2[CH2:20][CH2:19][CH2:18][C@@H:17]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH2:16]2)=O)[C@H:10]([NH2:29])[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]([CH2:13][N:15]2[CH2:20][CH2:19][CH2:18][C@@H:17]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH2:16]2)[C@H:10]([NH2:29])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 69748708(3S,4R)-3-Amino-4-[(S)-3-(4-fluorobenzyl)-piperidine-1-carbonyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 69747056(3S,4S)-3-amino-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 41.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(3S,4R)-3-Amino-4-[(S)-3-(4-fluorobenzyl)-piperidine-1-carbonyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (75 mg, 185 μmol) was treated with borane-tetrahydrofuran complex in tetrahydrofuran (1.0 M; 7.4 mL, 7.4 mmol) and stirred for 20 h . The mixture was treated slowly with 20% acetic acid in methanol (10 mL), and the resulting mixture was stirred at room temperature for 1 h . The solvents were removed, and the residue was dissolved in water, made basic (pH 11) with 50% sodium hydroxide, and extracted with methylene chloride. The combined organic phases were dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (5% methanol/dichloromethane) to provide the product (30 mg, 40%). 1H NMR (300 mHz, CD3OD) δ7.20 (m, 2H), 6.98 (m, 2H), 3.18-2.42 (15H), 1.80-1.50 (4H), 1.41 (s, 9H); mass spec. (ES+) m/z 392.4.

Workup

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

Sources & evidence

ORD record
ord-55e0762214084fc6a498fcde9599ecbd
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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