Triethylamine → Carbonic acid 3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indol-1-ylmethyl ester 4-nitro-phenyl ester

HRID 585158Notes

Reaction equation

HRID 585158 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C@@:8]2([F:24])[C:16]3[C:11](=[CH:12][C:13]([C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=3)[N:10]([CH2:21][OH:22])[C:9]2=[O:23])[CH:7]=1.C(N(CC)CC)C.Cl[C:35]([O:37][C:38]1[CH:43]=[CH:42][C:41]([N+:44]([O-:46])=[O:45])=[CH:40][CH:39]=1)=[O:36]>ClCCl>[N+:44]([C:41]1[CH:40]=[CH:39][C:38]([O:37][C:35](=[O:36])[O:22][CH2:21][N:10]2[C:11]3[C:16](=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:18])[F:19])[CH:12]=3)[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:25][CH3:26])([F:24])[C:9]2=[O:23])=[CH:43][CH:42]=1)([O-:46])=[O:45]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 821294-Nitrophenyl chloroformateHCID 69331104HCID 69331104, compound

Product 1

HCID 20822786Carbonic acid 3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indol-1-ylmethyl ester 4-nitro-phenyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 25 mL round bottom flask containing (S)-3-(5-chloro-2-methoxy-phenyl)-3-fluoro-1-hydroxymethyl-6-trifluoromethyl-1,3-dihydro-indol-2-one ((S)-IV) (0.397 g, 1.02 mmol) was added 5 mL anhydrous dichloromethane, triethylamine (0.204 g, 2.04 mmol), and 4-nitrophenyl chloroformate (0.246 g, 1.22 mmol). The reaction was allowed to stir overnight at room temperature, affording carbonic acid 3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indol-1-ylmethyl ester 4-nitro-phenyl ester (VIII), after which 2-aminoethanol (0.186 g, 3.05 mmol) was added and the reaction was allowed to stir for an additional 24 hours. The solvent was removed in vacuo, and the crude residue was purified by column chromatography (silica gel; 1:1 Hex:EtOAc to 4:1 EtOAc:Hex) producing 0.250 g (51%) of the title compound. 1H NMR (CDCl3 400 MHz): δ=7.78 (s,1H), 7.51 (s, 1H), 7.33 (d, 2H, J=7 Hz), 7.22 (d, 1H, J=7 Hz), 6.74 (d, 1H, J=7 Hz), 5.88 (d, 1H, J=12 Hz), 5.83 (d, 1H, J=12 Hz), 3.75 (m, 2H), 3.50 (s, 3H), 3.39 (m, 2H, J=7 Hz).

Sources & evidence

ORD record
ord-21b5e8098a0e4276b4e2eca8f8c9678f
Source dataset
uspto-grants-2005_08
Patent number
US06930100B2

Reaction notes

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