Sodium hydride → 4-Bromo-2-methylphenethyl 3-cyano-4-(ethylsulfonyl)phenylcarbamate

HRID 735582Notes

Reaction equation

HRID 735582 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.[C:14]([C:16]1[CH:17]=[C:18]([NH:27][C:28](=O)[O:29]C2C=CC=CC=2)[CH:19]=[CH:20][C:21]=1[S:22]([CH2:25][CH3:26])(=[O:24])=[O:23])#[N:15]>C1COCC1>[C:14]([C:16]1[CH:17]=[C:18]([NH:27][C:28](=[O:29])[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:19]=[CH:20][C:21]=1[S:22]([CH2:25][CH3:26])(=[O:24])=[O:23])#[N:15]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 578428522-(4-Bromo-2-methylphenyl)ethanolHCID 68818495HCID 68818495, compound

Product 1

HCID 578428634-Bromo-2-methylphenethyl 3-cyano-4-(ethylsulfonyl)phenylcarbamateYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

NaH (230 mg, 4.4 mmol, 60% disperson in oil) was added portionwise to a solution of 30B (490 mg, 2.3 mmol) in THF (12 mL) and the mixture was stirred for 30 min. The solution was cooled to −40° C. and 25A (760 mg, 2.3 mmol) was added in one portion. The cooling bath was removed and the reaction was stirred for 2 h. The reaction mixture was cooled to −40° C. and quenched by the addition of NH4Cl (5 mL, sat. aq.). The resulting mixture was partitioned between water (50 mL) and EtOAc (100 mL). The organic phase 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 31A (745 mg, 72%) as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 1.94 (t, J=7.42 Hz, 3 H) 3.11 (s, 3 H) 4.19 (q, J=7.15 Hz, 2 H) 5.14 (t, J=6.87 Hz, 2 H) 7.99 (d, J=8.24 Hz, 1 H) 8.14 (dd, J=7.70, 2.20 Hz, 1 H) 8.21 (d, J=1.65 Hz, 1 H) 8.72-8.77 (m, 1 H) 8.79-8.84 (m, 1 H) 8.90 (d, J=2.20 Hz, 1 H).

Workup

  1. customThe cooling bath was removed
  2. stirringthe reaction was stirred for 2 h
  3. temperatureThe reaction mixture was cooled to −40° C.
  4. customquenched by the addition of NH4Cl (5 mL, sat. aq.)
  5. customThe resulting mixture was partitioned between water (50 mL) and EtOAc (100 mL)
  6. washThe organic phase washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromoatography (0 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f7ae8ed4af6f4083b5c89b48219983c1
Source dataset
uspto-grants-2009_09
Patent number
US07592331B2

Reaction notes

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