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

HRID 507052Notes

Reaction equation

HRID 507052 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([CH2:10][CH3:11])[C:7]([C:12]([F:15])([F:14])[F:13])=[CH:6][C:5]=1[N:16]([C:24]([O:26][CH:27]([CH3:29])[CH3:28])=[O:25])[CH2:17][CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21].CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1>[CH3:23][O:22][C:20]([CH:19]1[CH2:18][CH2:17][N:16]([C:24]([O:26][CH:27]([CH3:29])[CH3:28])=[O:25])[C:5]2[CH:6]=[C:7]([C:12]([F:14])([F:13])[F:15])[C:8]([CH2:10][CH3:11])=[CH:9][C:4]=2[C:3]1=[O:2])=[O:21]

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 594325265-Ethyl-2-[isopropoxycarbonyl-(3-methoxycarbonyl-propyl)-amino]-4-trifluoromethyl-benzoic acid methyl ester

Product 1

HCID 594324487-Ethyl-5-oxo-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1,4-dicarboxylic acid 1-isopropyl ester 4-methyl esterYield 85%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a 0° C. cooled solution of 5-ethyl-2-[isopropoxycarbonyl-(3-methoxycarbonyl-propyl)-amino]-4-trifluoromethyl-benzoic acid methyl ester (39.72 g, 91.64 mmol) in toluene add potassium tert-butoxide (24.68 g, 219.92 mmol). Stir the mixture at room temperature for 30 min under an atmosphere of N2. Quench the mixture with 2 N HCl (150 mL) and dilute with ethyl acetate (1.5 L). Wash with water (2×400 mL) and brine (500 mL). Dry the organic layer over anhydrous sodium sulfate and filter through Celite to provide the title compound as a yellow viscous oil (31.25 g, 85%): TLC Rf 0.63 (3:1 hexanes/ethyl acetate); 1H NMR (CDCl3, 300 MHz) δ 1.0-1.40 (m, 9H), 2.31-2.55 (m, 2H), 2.88-2.94 (m, 1H), 3.75 (s, 3H), 3.89 (s, 3H), 4.89-4.93 (m, 1H), 5.11-5.12 (m, 1H), 7.43 (s, 1H), 7.91 (s, 1H).

Workup

  1. customQuench the mixture with 2 N HCl (150 mL)
  2. additiondilute with ethyl acetate (1.5 L)
  3. washWash with water (2×400 mL) and brine (500 mL)
  4. dry with materialDry the organic layer over anhydrous sodium sulfate
  5. filtrationfilter through Celite

Sources & evidence

ORD record
ord-d3724f3affa044b881b4ce641cd4f8e7
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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