Sodium hydride → 4-Bromo-2-methylphenethyl 3-cyanophenylcarbamate

HRID 735577Notes

Reaction equation

[H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][OH:12])=[C:6]([CH3:13])[CH:5]=1.[N:14]([C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=1)[C:20]#[N:21])=[C:15]=[O:16]>C1COCC1>[C:20]([C:19]1[CH:18]=[C:17]([NH:14][C:15](=[O:16])[O:12][CH2:11][CH2:10][C:7]2[CH:8]=[CH:9][C:4]([Br:3])=[CH:5][C:6]=2[CH3:13])[CH:24]=[CH:23][CH:22]=1)#[N:21]

Participants

Conditions

Temperature: -78 °C

Procedure

NaH (150 mg, 60% disperson in oil) was added portionwise to a solution of 30B (570 mg, 2.65 mmol) in THF (26.5 mL) and the mixture was stirred for 30 min. The solution was cooled to −78° C. and 3-isocyanatobenzonitrile (382 mg, 2.65 mmol) was added in one portion. The cooling bath was removed and the reaction was stirred for 2 h. Water (100 mL) was added to the reaction mixture and it was extracted with EtOAc (2×75 mL). The organics were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromoatography (0 to 100% EtOAc in hexanes) to yield 30C (590 mg, 62%). 1H NMR (400 MHz, DMSO-D6) δ ppm 2.30 (s, 3 H) 2.92 (t, J=6.95 Hz, 2 H) 4.28 (t, J=6.95 Hz, 2 H) 7.17 (d, J=8.34 Hz, 1 H) 7.32 (dd, J=8.21, 1.89 Hz, 1 H) 7.39 (d, J=1.77 Hz, 1 H) 7.41-7.55 (m, 2 H) 7.70 (d, J=8.08 Hz, 1 H) 7.85 (s, 1 H) 9.97 (s, 1 H).

Workup

customThe cooling bath was removed
stirringthe reaction was stirred for 2 h
additionWater (100 mL) was added to the reaction mixture and it
extractionwas extracted with EtOAc (2×75 mL)
washwashed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe crude product was purified by flash chromoatography (0 to 100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-335cf96d097445b48a96923f071bbcf3
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07592331B2

Reaction notes

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