Allyl Alcohol → Tert-butyl (2-chloro-5-cyano-3-(3-oxopropyl)phenyl)carbamate

HRID 921857Notes

Reaction equation

Br[C:2]1[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.C1(CNCC2CCCCC2)CCCCC1.[CH2:34]([OH:37])[CH:35]=[CH2:36]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1C)(C)(C)C.C(#N)C>[Cl:18][C:3]1[C:2]([CH2:36][CH2:35][CH:34]=[O:37])=[CH:7][C:6]([C:8]#[N:9])=[CH:5][C:4]=1[NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14]

Participants

Conditions

Temperature: 90 °C

Procedure

Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (500 mg, 1.508 mmol), 2-(di-t-butylphosphino)-2′-methylbiphenyl (14.13 mg, 0.045 mmol), and Pd2(dba)3 (13.81 mg, 0.015 mmol) were combined in a 40 dram vial which was evacuated and backfilled 3× with N2. To this was added acetonitrile (3 mL), N,N-dicyclohexylmethylamine (0.388 mL, 1.809 mmol), and prop-2-en-1-ol (0.154 mL, 2.262 mmol). The vial was again evacuated and backfilled with N2 3×, and heated at 90° C. for 3 h. The reaction mixture was cooled to room temperature and the solvent removed in vacuo. The material was purified by flash column chromatography (0%-50% EtOAc/Hex; 80 g column). Tert-butyl (2-chloro-5-cyano-3-(3-oxopropyl)phenyl)carbamate (184 mg) was obtained as a yellow glass.

Workup

customwas evacuated
customThe vial was again evacuated
temperatureThe reaction mixture was cooled to room temperature
customthe solvent removed in vacuo
customThe material was purified by flash column chromatography (0%-50% EtOAc/Hex; 80 g column)

Sources & evidence

ORD record: ord-23f0b7c69d2841d8b029b3209cbfe4e0
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273057B2

Reaction notes

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