Dimethylformamide → (3-Chloro-5-cyano-2-fluoro-benzyl)-carbamic acid tert-butyl ester

HRID 1527473Notes

Reaction equation

[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[CH:14]=[C:13](Br)[CH:12]=[C:11]([Cl:16])[C:10]=1[F:17])([CH3:4])([CH3:3])[CH3:2].[CH3:19][N:20](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([C:19]#[N:20])[CH:12]=[C:11]([Cl:16])[C:10]=1[F:17])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of (5-bromo-3-chloro-2-fluoro-benzyl)-carbamic acid tert-butyl ester (3 g, 8.86 mmol) in DMF (45 mL) was added zinc cyanide (1.04 g, 8.86 mmol) and Pd(Ph3P)4 (1.02 g, 0.886 mmol). The reaction mixture was stirred at 120° C. for 15 min in a microwave apparatus (Personal Chemistry, Biotage). After cooling to RT, the mixture was filtered through Celite and rinsed down with EtOAc. The filtrate was washed with saturated aqueous NH4Cl solution (4×75 mL), dried (Na2SO4) and evaporated in vacuo. Purification by flash column chromatography on silica gel (eluent gradient: c-hexane/EtOAc 9:1 to 3:1) afforded the title compound as white solid. TLC Rf (c-hexane/EtOAc 3:1)=0.35; tR (HPLC conditions c): 5.28 min.

Workup

temperatureAfter cooling to RT
filtrationthe mixture was filtered through Celite
washrinsed down with EtOAc
washThe filtrate was washed with saturated aqueous NH4Cl solution (4×75 mL)
dry with materialdried (Na2SO4)
customevaporated in vacuo
customPurification by flash column chromatography on silica gel (eluent gradient: c-hexane/EtOAc 9:1 to 3:1)

Sources & evidence

ORD record: ord-abc2ebf9d0604c8ba7cf414ddde6e604
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085555B2

Reaction notes

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