Trifluoroacetic acid → (R)-4-biphenyl-4-yl-3-(3-carboxy-propionylamino)-butyric acid ethyl ester

HRID 1945042Notes

Reaction equation

HRID 1945042 reaction equation
[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C@H:6]([NH:20][C:21](OC(C)(C)C)=[O:22])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)[CH3:2].C(O)(C(F)(F)F)=O.C1(=O)[O:41][C:39](=[O:40])[CH2:38][CH2:37]1>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C@H:6]([NH:20][C:21](=[O:22])[CH2:37][CH2:38][C:39]([OH:41])=[O:40])[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:12][CH:13]=1)[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 7922Succinic anhydrideHCID 59607632(R)-ethyl 4-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)butanoate

Product 1

HCID 49822223(R)-4-biphenyl-4-yl-3-(3-carboxy-propionylamino)-butyric acid ethyl esterYield 50.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-4-biphenyl-4-yl-3-tert-butoxycarbonylamino-butyric acid ethyl ester (400 mg, 1.04 mmol) in DCM (10 mL) at room temperature is added TFA (2.009 mL, 26.1 mmol) and the mixture is stirred at room temperature for 1 hour. The mixture is concentrated under reduced pressure. To the obtained TFA salt in DCM (10 mL) at ice bath temperature is added succinic anhydride (125 mg, 1.25 mmol) and followed by TEA (0.363 mL, 2.61 mmol). The reaction is stirred at room temperature for 16 hours. The mixture is concentrated under reduced pressure. The obtained residue is purified by flash chromatography (silica gel, 2% to 5% EtOH/DCM) give (R)-4-biphenyl-4-yl-3-(3-carboxy-propionylamino)-butyric acid ethyl ester (200 mg). HPLC retention time=1.53 minutes (condition C); MS=384 (m+1).

Workup

  1. concentrationThe mixture is concentrated under reduced pressure
  2. stirringThe reaction is stirred at room temperature for 16 hours
  3. concentrationThe mixture is concentrated under reduced pressure
  4. customThe obtained residue is purified by flash chromatography (silica gel, 2% to 5% EtOH/DCM)

Sources & evidence

ORD record
ord-774cdea8f81045c4b8e9b8b55df6870b
Source dataset
uspto-grants-2013_03
Patent number
US08394853B2

Reaction notes

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