Benzyl chloroformate → 8-Bromo-6-chloro-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid benzyl ester

HRID 388274Notes

Reaction equation

HRID 388274 reaction equation
Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[Br:12][C:13]1[C:22]2[O:21][CH2:20][CH2:19][NH:18][C:17]=2[CH:16]=[C:15]([Cl:23])[CH:14]=1.[OH-].[Na+]>C(OCC)(=O)C>[CH2:5]([O:4][C:2]([N:18]1[C:17]2[CH:16]=[C:15]([Cl:23])[CH:14]=[C:13]([Br:12])[C:22]=2[O:21][CH2:20][CH2:19]1)=[O:3])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 225572348-Bromo-6-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazine

Product 1

HCID 207656808-Bromo-6-chloro-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid benzyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Benzyl chloroformate (1.877 g, 0.011 mol) was added dropwise to a solution of 8-bromo-6-chloro-3,4-dihydro-2H-benzo[1,4]oxazine (2.85 g, 0.01 mol) in a 1:1 mixture of ethyl acetate (30 mL) and 10% aqueous sodium hydroxide (30 mL). After 3 hours at ambient temperature, the layers were separated and the organic phase was washed with water (2×50 mL), saturated aqueous sodium bicarbonate (50 mL), dried (K2CO3) and concentrated in vacuo and the residue was purified by column chromatography on silica gel (eluting with hexane-ethyl acetate; 7:3, V/V) to give 8-bromo-6-chloro-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid benzyl ester as an oil (3.47 g, 98%). A sample was recrystallized from ethanol-water. MS: MH+ 383. M.P. 95.0-97.7° C.

Workup

  1. customthe layers were separated
  2. washthe organic phase was washed with water (2×50 mL), saturated aqueous sodium bicarbonate (50 mL)
  3. dry with materialdried (K2CO3)
  4. concentrationconcentrated in vacuo
  5. customthe residue was purified by column chromatography on silica gel (eluting with hexane-ethyl acetate; 7:3, V/V)

Sources & evidence

ORD record
ord-1d03815bb4174469a26b644b3419d15c
Source dataset
uspto-grants-2013_02
Patent number
US08377931B2

Reaction notes

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