Methanol → Methyl (1R,3S)-1-amino-3-(4-bromophenyl)cyclopentane-1-carboxylate hcl

HRID 2199460Notes

Reaction equation

HRID 2199460 reaction equation
[NH2:1][C:2]1([C:14]([OH:16])=[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.O=S(Cl)[Cl:19].[CH3:21]O>O.CCOC(C)=O>[ClH:19].[NH2:1][C@:2]1([C:14]([O:16][CH3:21])=[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

Participants

6

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 86730031(3S)-1-amino-3-(4-bromophenyl)cyclopentane-1-carboxylic acid

Product 1

HCID 44191914Methyl (1R,3S)-1-amino-3-(4-bromophenyl)cyclopentane-1-carboxylate hcl

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of (3S)-1-amino-3-(4-bromophenyl)cyclopentanecarboxylic acid (10.2 g, 35.9 mmol) in MeOH (100 mL) was cooled in an ice bath, followed by addition of SOCl2 (15.72 mL, 215 mmol) dropwise. After the addition was complete, the solution was refluxed for 3 hrs at which time the reaction was determined to be complete by HPLC. The solution was concentrated to remove methanol to afford a solid. The solid was taken in 50 ml of 3% H2O in EtOAc and stirred well for 30 mins. The white solid formed was collected by filtration. The wet white solid was taken in 50 ml of 4% H2O in 1,2-dimethoxyethane and heated to 50° C. for 3 hrs, and then stirred at room temperature overnight. The resulting white solid was collected by filtration and dried to afford (1R,3S)-methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate hydrochloride (3.5 g, 10.35 mmol). HPLC retention time=6.6 min (Condition H) LC/MS M+1=298/300. 1H NMR (400 MHz, DMSO-d6) δ 8.95 (br. s, 3H) 7.50-7.53 (m, 2H), 7.35-7.37 (m, 2H), 3.81 (s, 3H) 3.17-3.28 (m, 1H), 2.57 (dd, J=14, 7 Hz, 1H), 2.0-2.28 (m, 5H).

Workup

  1. additionAfter the addition
  2. temperaturethe solution was refluxed for 3 hrs at which time the reaction
  3. concentrationThe solution was concentrated
  4. customto remove methanol
  5. customto afford a solid
  6. customThe white solid formed
  7. filtrationwas collected by filtration
  8. stirringstirred at room temperature overnight
  9. filtrationThe resulting white solid was collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-2603d492c3c24589ba6256b891d95077
Source dataset
uspto-grants-2016_06
Patent number
US09359286B2

Reaction notes

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