Water → benzyl [(1S)-2-cyano-2-hydroxy-1-methylethyl]carbamate

HRID 1994582Notes

Reaction equation

[C-:1]#[N:2].[CH3:3][C@H:4]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH:5]=[O:6].[NH4+].[Cl-].O>C1(C)C=CC=CC=1>[C:1]([CH:5]([OH:6])[C@@H:4]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:3])#[N:2]

Participants

Conditions

Temperature: -78 °C

Procedure

Diethylalumninum cyanide (4.53 mL, 1M in toluene, 4.53 mmol) was added dropwise to a stirred solution of benzyl [(1S)-1-methyl-2-oxoethyl]carbamate (0.853 g, 4.12 mmol) in dry toluene (33 mL) at −78° C. under N2. The mixture was stirred at −78° C. for 6 h and then allowed to warm to room temperature overnight. Saturated NH4Cl (20 mL) and water (10 mL) were added then the mixture was extracted with EtOAc (3×50 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to afford the crude product. This was purified by flash chromatography (Si, 40×160 mm, 0-40% EtOAc in hexanes gradient) to afford benzyl [(1S)-2-cyano-2-hydroxy-1-methylethyl]carbamate as a 3:1 mixture of diastereoisomers. Rf=0.63 (50% EtOAc in hexanes). LCMS calc.=257.1; found=257.1 (M+1)+. 1H NMR (500 MHz, CDCl3) major diastereoisomer: δ 7.39-7.31 (m, 5H), 5.11 (m, 2H), 4.60 br (s, 1H), 3.96 (m, 1H), 1.34 (d, J=6.7 Hz, 3H), minor diastereoisomer: δ 7.39-7.31 (m, 5H), 5.14 (m, 2H), 4.50 br (s, 1H), 4.10 (m, 1H), 1.30 (d, J=7.0 Hz, 3H).

Workup

temperatureto warm to room temperature overnight
extractionthe mixture was extracted with EtOAc (3×50 mL)
dry with materialThe combined extracts were dried (Na2SO4)
concentrationconcentrated in vacuo
customto afford the crude product
customThis was purified by flash chromatography (Si, 40×160 mm, 0-40% EtOAc in hexanes gradient)

Sources & evidence

ORD record: ord-f394e0c685d6490d8124668ae5e2d5f3
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07652049B2

Reaction notes

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