Acetone Cyanohydrin → 1,1-Dimethylethyl (3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-[(1-methylethyl)amino]butanoate

HRID 1160403Notes

Reaction equation

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

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 1,1-dimethylethyl (3S)-4-amino-3-[(3-chloro-4-cyanophenyl)amino]butanoate (0.309 g, 1 mmol), acetone cyanohydrin (0.1 g, 1.18 mmol) and crushed 4 Å molecular sieves in EtOH (5 mL) was stirred at 60° C. for 6 h. After cooled down, the reaction mixture was filtered. The filtrate was treated with NaBH4 (excess amount) and stirred for 2.5 h. The reaction was diluted with H2O and extracted with Et2O (2×). The organic extracts were washed with H2O (2×), dried over Na2SO4, filtered, and concentrated to yield the titled product (0.33 g, 94%). LC-MS (ES) m/e 352.5 (M+H)+.

Workup

temperatureAfter cooled down
filtrationthe reaction mixture was filtered
additionThe filtrate was treated with NaBH4 (excess amount)
stirringstirred for 2.5 h
additionThe reaction was diluted with H2O
extractionextracted with Et2O (2×)
washThe organic extracts were washed with H2O (2×)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-ea74e2e89dea42b4ab495bd56349f31b
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07816395B2

Reaction notes

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