Trifluoroacetic acid → (R)-3-amino-4-(3'-chloro-biphenyl-4-yl)-2-methyl-butyric acid ethyl ester trifluoroacetate

HRID 1945098

Reaction equation

HRID 1945098 reaction equation
[CH2:1]([O:3][C:4](=[O:30])[C@H:5]([CH3:29])[CH:6]([NH:21]C(OC(C)(C)C)=O)[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=2)=[CH:10][CH:9]=1)[CH3:2].[C:31]([OH:37])([C:33]([F:36])([F:35])[F:34])=[O:32]>C(Cl)Cl>[F:34][C:33]([F:36])([F:35])[C:31]([OH:37])=[O:32].[CH2:1]([O:3][C:4](=[O:30])[C@H:5]([CH3:29])[CH:6]([NH2:21])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=2)=[CH:10][CH:9]=1)[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67208757(R)-3-tert-butoxycarbonylamino-4-(3'-chloro-biphenyl-4-yl)-2-methyl-butyric acid ethyl ester

Product 1

HCID 68423502(R)-3-amino-4-(3'-chloro-biphenyl-4-yl)-2-methyl-butyric acid ethyl ester trifluoroacetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-3-tert-butoxycarbonylamino-4-(3′-chloro-biphenyl-4-yl)-butyric acid ethyl ester (300 mg, 0.718 mmol) in THF (10 ml) at −78° C. is added LiHMDS/THF (1M) (1.579 ml, 1.579 mmol). The reaction mixture is stirred at −78° C. for 50 min and then to this mixture is added methyl iodine (0.054 ml, 0.861 mmol) and the reaction is slowly warmed up to room temperature and stirred over night. The reaction is quenched by sat. NH4Cl and is extracted with EtOAc. The combined organic layer is washed with brine and dried over anhydrous sodium sulfate, filtered and concentrated to give the crude. Reverse phase HPLC [20 to 90% ACN—H2O (0.1% TFA) over 10 min by Sunfire C18] give (R)-3-tert-butoxycarbonylamino-4-(3′-chloro-biphenyl-4-yl)-2-methyl-butyric acid ethyl ester. LCMS (condition B): 432 (M+1); retention time=1.55 min. To a solution of (R)-3-tert-butoxycarbonylamino-4-(3′-chloro-biphenyl-4-yl)-2-methyl-butyric acid ethyl ester (240 mg, 0.556 mmol) in DCM (2 ml) at room temperature was added TFA (1.070 ml, 13.89 mmol) and the mixture is stirred at room temperature. 1 hr the reaction is done so the mixture is concentrated to give (R)-3-amino-4-(3′-chloro-biphenyl-4-yl)-2-methyl-butyric acid ethyl ester trifluoroacetate. LCMS (condition B): 332 (M+1); retention time=1.00 min.

Workup

  1. custom1 hr
  2. concentrationis concentrated

Sources & evidence

ORD record
ord-f4bfbdd47df243e5886d7e4e5b27850a
Source dataset
uspto-grants-2013_03
Patent number
US08394853B2

Linked notes

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