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Ethyl Acetate → 5-{[1-(2-Chloro-3-fluoro-4-hydroxyphenyl)-3,3,3-trifluoro-2-hydroxy-2-(hydroxymethyl)-propyl]amino}-7-fluoro-1H-quinolin-2-one

HRID 1191622
Notes
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Reaction equation

HRID 1191622 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[C:6]([O:9]C)[CH:5]=[CH:4][C:3]=1[CH:11]([NH:21][C:22]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]2[C:23]=1[CH:24]=[CH:25][C:26](=[O:33])[NH:27]2)[C:12]([OH:20])([CH2:17][O:18]C)[C:13]([F:16])([F:15])[F:14].B(Br)(Br)Br.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>ClCCl>[Cl:1][C:2]1[C:7]([F:8])=[C:6]([OH:9])[CH:5]=[CH:4][C:3]=1[CH:11]([NH:21][C:22]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]2[C:23]=1[CH:24]=[CH:25][C:26](=[O:33])[NH:27]2)[C:12]([OH:20])([CH2:17][OH:18])[C:13]([F:16])([F:14])[F:15]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 426014695-{[1-(2-Chloro-3-fluoro-4-methoxyphenyl)-3,3,3-trifluoro-2-hydroxy-2-(methoxymethyl)propyl]amino}-7-fluoro-1H-quinolin-2-one

Product 1

HCID 426233495-{[1-(2-Chloro-3-fluoro-4-hydroxyphenyl)-3,3,3-trifluoro-2-hydroxy-2-(hydroxymethyl)-propyl]amino}-7-fluoro-1H-quinolin-2-one
Yield 17.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 100 mg (0.20 mmol) of 5-{[1-(2-Chloro-3-fluoro-4-methoxyphenyl)-3,3,3-trifluoro-2-hydroxy-2-(methoxymethyl)propyl]amino}-7-fluoro-1H-quinolin-2-one of example 5 in 8.6 dichloromethane at −30° C. are added 1.6 ml of a 1M solution of boron tribromide in dichloromethane under argon. The reaction mixture is stirred for 16 hours in a temperature range of between 0° C. and 25° C. The reaction mixture is mixed at 0° C. with saturated sodium bicarbonate solution. After dilution with ethyl acetate the batch is allowed to come to room temperature, stirred for 10 minutes and phases are separated. The aqueous phase is acidified with 4 M HCl and extracted with 10% methanol in dichloromethane. After removal of the solvent preparative thin layer chromatography on silica gel (ethyl acetate/methanol 4:1) yields 16 mg of the title compound.

Workup

  1. customto come to room temperature
  2. stirringstirred for 10 minutes
  3. customphases are separated
  4. extractionextracted with 10% methanol in dichloromethane
  5. customAfter removal of the solvent preparative thin layer chromatography on silica gel (ethyl acetate/methanol 4:1)

Sources & evidence

ORD record
ord-4c384d67a1ff4b09aa767a207ffd87bf
Source dataset
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08680117B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes