Sodium hydride → HCID 178502726, compound

HRID 579564Notes

Reaction equation

HRID 579564 reaction equation
[CH3:1][O:2][N:3]([CH3:23])[C:4]([C@@H:6]1[CH2:11][CH2:10][C@H:9]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:8][CH2:7]1)=[O:5].[H-].[Na+].[Cl:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Br)=[CH:29][CH:28]=1>CN(C=O)C>[Cl:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31][N:12]([C@H:9]2[CH2:10][CH2:11][C@@H:6]([C:4](=[O:5])[N:3]([O:2][CH3:1])[CH3:23])[CH2:7][CH2:8]2)[C:13](=[O:22])[O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 178502728HCID 178502728, compound

Product 1

HCID 178502726HCID 178502726, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of benzyl cis-4-(methoxy(methyl)carbamoyl)cyclohexylcarbamate in DMF (12 mL) under an atmosphere of nitrogen was cooled to 0° C., followed by treatment with sodium hydride (150 mg of 60 wt % NaH in oil, 3.75 mmol). After stirring at room temperature for 30 min, the reaction mixture was cooled to 0° C. and charged with 4-chlorobenzyl bromide (793 g, 3.75 mmol). The resulting solution was warmed slowly to room temperature and stirred for another 16 hr prior to partitioning of the solution between saturated aqueous NaHCO3 and ethyl acetate. The aqueous layer was further extracted with additional ethyl acetate. After separating the organic layer, the combined organic layer was washed with saturated aqueous sodium chloride, dried using MgSO4, filtered, and concentrated to give benzyl 4-chlorobenzyl(cis-4-(methoxy(methyl)carbamoyl)cyclohexyl)carbamate as a colorless oil (1.19 g, 2.67 mmol, 86.0%). 1H NMR (CDCl3, 300 MHz) δ 7.45-7.05 (m, 9H), 5.09 (bs, 2H), 4.41 (bs, 2H), 4.30-4.04 (m, 1H), 3.65 (s, 3H), 3.14 (s, 3H), 2.91 (m, 1H), 2.02-1.84 (m, 4H), 1.70-1.47 (m, 4H).

Workup

  1. temperaturethe reaction mixture was cooled to 0° C.
  2. temperatureThe resulting solution was warmed slowly to room temperature
  3. stirringstirred for another 16 hr
  4. customto partitioning of the solution between saturated aqueous NaHCO3 and ethyl acetate
  5. extractionThe aqueous layer was further extracted with additional ethyl acetate
  6. customAfter separating the organic layer
  7. washthe combined organic layer was washed with saturated aqueous sodium chloride
  8. customdried
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-5c27325e29ab4960954d9a135f636937
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

Loading…