Ammonia → 2-[(R)-(Carbamoylphenylmethyl)-amino]-3-(4-methoxyphenyl)-2-(S)-methylpropionamide

HRID 78949

Reaction equation

[C:1]([C@:3]([NH:14][C@H:15]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:16]([NH2:18])=[O:17])([CH3:13])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=1)#[N:2].C(Cl)Cl.[OH:28]S(O)(=O)=O.N>CCOC(C)=O>[C:16]([C@H:15]([NH:14][C@@:3]([CH3:13])([CH2:4][C:5]1[CH:6]=[CH:7][C:8]([O:11][CH3:12])=[CH:9][CH:10]=1)[C:1]([NH2:2])=[O:28])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)(=[O:17])[NH2:18]

Participants

Conditions

Temperature: -10 °C

Procedure

To a 500 mL flask were added nitrile 2 (10.0 g, 30.95 mmol) and CH2Cl2 (130 mL). The solution was cooled to −10° C. and H2SO4 (10 mL) was added dropwise over 15 min. The mixture was stirred for 2 h at 0° C. Ice (200 g) was added and the mixture was stirred for 1 h. The mixture was basified with 32% aq NH3 to pH 8-9, EtOAc (400 mL) was added and the phases were separated. The aqueous phase was extracted with EtOAc (2×250 mL). The combined organic phases were dried over MgSO4 and were concentrated to provide 3 (11.1 g (9.99 g theoretical, the sample contains 10% w/w of EtOAc by NMR) 94%, 92.9% chemical purity, 97% de by HPLC/MS) as a white solid. HPLC/MS tR=3.04 min; m/z=342.1 (M+1)

Workup

stirringthe mixture was stirred for 1 h
additionwas added
customthe phases were separated
extractionThe aqueous phase was extracted with EtOAc (2×250 mL)
dry with materialThe combined organic phases were dried over MgSO4
concentrationwere concentrated
customto provide 3 (11.1 g (9.99 g theoretical

Sources & evidence

ORD record: ord-5b7042aa79594fc7986d5d8042e1dca5
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841486B2

Linked notes

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