Hydrochloric Acid → (R)-ethyl 3-amino-4-(biphenyl-4-yl)butanoate hydrochloride

HRID 881804

Reaction equation

HRID 881804 reaction equation
[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C@H:6]([NH:20]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]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)[CH3:2].[ClH:29].O1CCOCC1>>[ClH:29].[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C@H:6]([NH2:20])[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

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 59607632(R)-ethyl 4-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)butanoate

Product 1

HCID 68424075(R)-ethyl 3-amino-4-(biphenyl-4-yl)butanoate hydrochloride

Procedure

To (R)-ethyl-4-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)butanoate (230.1 mg, 0.600 mmol) is added a solution of HCl in 1,4-dioxane (3.00 mL, 12.00 mmol) at room temperature. After stirring for 1 hour, the reaction mixture is concentrated under reduced pressure to give (R)-3-amino-4-biphenyl-4-yl-butyric acid ethyl ester hydrochloride. A solution of (R)-3-amino-4-biphenyl-4-yl-butyric acid ethyl ester hydrochloride, succinic anhydride (72.1 mg, 0.720 mmol) and DIPEA (0.126 mL, 0.720 mmol) in dichloromethane (4 mL) is allowed to stir for 1 hour. The reaction is quenched with 10% aqueous citric acid and extracted with dichloromethane. The organic layer is separated and concentrated under reduced pressure. The obtained residue is purified by flash column chromatography on CN-modified silica gel (eluent: heptane/EtOAc=100:0 to 0:100) and by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN) to give (R)-4-(1-(biphenyl-4-yl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoic acid (148.2 mg). HPLC retention time=1.64 minutes (condition A); MS (m+1)=384.1; 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 1.21 (t, J=7.07 Hz, 3 H) 2.31-2.39 (m, 2 H) 2.40-2.56 (m, 4 H) 2.77-2.92 (m, 2 H) 4.08 (q, J=7.24 Hz, 2 H) 4.33-4.48 (m, 1 H) 6.62 (d, J=8.34 Hz, 1 H) 7.30 (d, J=8.08 Hz, 2 H) 7.32-7.39 (m, 1 H) 7.41-7.49 (m, 2 H) 7.54-7.60 (m, 2H) 7.60-7.67 (m, 2 H) 10.02 (br. s., 1 H).

Workup

  1. concentrationthe reaction mixture is concentrated under reduced pressure

Sources & evidence

ORD record
ord-bfc92cf409e84d7293cf9fb4581ee97e
Source dataset
uspto-grants-2015_03
Patent number
US08993631B2

Linked notes

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