Sodium borohydride → ((1R,3R)-1-amino-3-(4-bromophenyl)cyclopentyl)methanol

HRID 2199465Notes

Reaction equation

HRID 2199465 reaction equation
[NH2:1][C@:2]1([C:14](OC)=[O:15])[CH2:6][CH2:5][C@@H:4]([C:7]2[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=2)[CH2:3]1.[BH4-].[Na+]>CO>[NH2:1][C@:2]1([CH2:14][OH:15])[CH2:6][CH2:5][C@@H:4]([C:7]2[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=2)[CH2:3]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydride2×HCID 25002100(1R,3R)-methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate

Product 1

HCID 68263296((1R,3R)-1-amino-3-(4-bromophenyl)cyclopentyl)methanolYield 90.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(1R,3R)-Methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate (1-2, 3.88 g, 13.01 mmol) was dissolved in MeOH (65.1 ml) and sodium borohydride (1.477 g, 39.0 mmol) was added portionwise. Additional sodium borohydride was added (0.5 equiv every 1 h) portionwise until the reaction was determined to be complete by HPLC analysis. The reaction was found to be complete after 2 hours. The reaction mixture was quenched with water and diluted with ethyl acetate. The aqueous layer was back extracted three times with EtOAc. The organic layers were combined, washed with saturated NaCl, dried over MgSO4, filtered and concentrated to afford ((1R,3R)-1-amino-3-(4-bromophenyl)cyclopentyl)methanol (3.19 g, 11.81 mmol). HPLC ret time=0.68 min; LC/MS M+1=272: 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J=8.4 Hz, 2H), 7.13 (d, J=8.4 Hz, 2H), 3.49 (s, 2H), 3.32-3.41 (m, 1H), 2.19-2.25 (m, 1H), 1.98-2.07 (m, 1H), 1.90-1.95 (m, 1H), 1.66-1.74 (m, 2H), 1.52-1.60 (m, 1H).

Workup

  1. customThe reaction mixture was quenched with water
  2. additiondiluted with ethyl acetate
  3. extractionThe aqueous layer was back extracted three times with EtOAc
  4. washwashed with saturated NaCl
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-97b1567d8c714e47843d0a7854a0f426
Source dataset
uspto-grants-2016_06
Patent number
US09359286B2

Reaction notes

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