Potassium tert-butoxide → 7-Bromo-8-chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1,4-dicarboxylic acid 1-isopropyl ester 4-methyl ester

HRID 2353910Notes

Reaction equation

HRID 2353910 reaction equation
CC(C)([O-])C.[K+].CO[C:9](=[O:32])[C:10]1[CH:15]=[C:14]([Br:16])[C:13]([Cl:17])=[CH:12][C:11]=1[N:18]([C:26]([O:28][CH:29]([CH3:31])[CH3:30])=[O:27])[CH2:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:25][O:24][C:22]([CH:21]1[CH2:20][CH2:19][N:18]([C:26]([O:28][CH:29]([CH3:30])[CH3:31])=[O:27])[C:11]2[CH:12]=[C:13]([Cl:17])[C:14]([Br:16])=[CH:15][C:10]=2[C:9]1=[O:32])=[O:23]

Participants

5

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 686803425-Bromo-4-chloro-2-[isopropoxycarbonyl-(3-methoxycarbonyl-propyl)-amino]-benzoic acid methyl ester

Product 1

HCID 686781067-Bromo-8-chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1,4-dicarboxylic acid 1-isopropyl ester 4-methyl esterYield 62%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a heated mixture of potassium t-butoxide (1.27 g, 11.3 mmol) in toluene (50 ml) at 70° C. was added a solution of 5-Bromo-4-chloro-2-[isopropoxycarbonyl-(3-methoxycarbonyl-propyl)-amino]-benzoic acid methyl ester (2.55 g, 5.66 mmol) in toluene (50.0 ml) over 30 minutes. After the addition was completed, the mixture was cooled to room temperature and diluted with ethyl acetate (100 ml), and then washed with 1.00N HCl(aq) (120 ml) and brine (3×120 ml). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. Purification by silica gel chromatography (gradient eluent, 0-15% ethyl acetate in hexane) provided 7-Bromo-8-chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1,4-dicarboxylic acid 1-isopropyl ester 4-methyl ester (1.46 g, 62%) as oil. MS (ES+): 418, 420 (M+H).

Workup

  1. additionAfter the addition
  2. washwashed with 1.00N HCl(aq) (120 ml) and brine (3×120 ml)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customPurification by silica gel chromatography (gradient eluent, 0-15% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-e7ad46a0243141299f8a1d7f47ad1067
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

Loading…