Ethyl Acetate → 6-(3-Chloro-4-fluoro-phenyl)-8-fluoro-4,4-dimethyl-1,4-dihydrobenzo[d][1,3]oxazin-2-one

HRID 1634972

반응식

HRID 1634972 반응식
Br[C:2]1[CH2:3][CH:4]2[C:9]([CH3:11])([CH3:10])[O:8][C:7](=[O:12])[NH:6][C:5]2=[C:13]([F:15])[CH:14]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][C:18]=1[Cl:26].C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:26][C:18]1[CH:19]=[C:20]([C:2]2[CH:14]=[C:13]([F:15])[C:5]3[NH:6][C:7](=[O:12])[O:8][C:9]([CH3:11])([CH3:10])[C:4]=3[CH:3]=2)[CH:21]=[CH:22][C:17]=1[F:16]

참가 물질

8

반응물 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 688225046-Bromo-8-fluoro-4,4-dimethyl-dihydro-benzo[d][1,3]oxazin-2-one

생성물 1

HCID 98584066-(3-Chloro-4-fluoro-phenyl)-8-fluoro-4,4-dimethyl-1,4-dihydrobenzo[d][1,3]oxazin-2-one수율 66%

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

A mixture of 6-bromo-8-fluoro-4,4-dimethyl-dihydro-benzo[d][1,3]oxazin-2-one (0.176 g, 0.64 mmol), 4-fluoro-3-chlorophenyl boronic acid (0.15 g, 0.84 mmol), tetrakis(triphenylphosphine)-palladium (0) (0.04 g, 0.032 mmol), and sodium carbonate (0.20 g, 1.92 mmol) in DME (10 mL) and water (5 mL) was subject to a blanket of nitrogen for 15 minutes at 50° C. and then was heated at 85° C. for 1 hour. The reaction mixture was cooled to room temperature and ethyl acetate (100 mL) was added. The organic layer was washed twice with aqueous ammonium chloride (100 mL) and once with brine (100 mL), dried over magnesium sulfate and concentrated. The residue was purified via chromatography (silica gel, 25% ethyl acetate/hexane) to give 6-(3-chloro-4-fluoro-phenyl)-8-fluoro-4,4-dimethyl-1,4-dihydrobenzo[d][1,3]oxazin-2-one as a white solid (0.13 g, 66%): mp 246-248° C.; 1H-NMR (DMSO-d6) δ10.5 (s, 1H), 8.00 (dd, 1H, J=7.09, 2.32 Hz), 7.78-7.73 (m, 1H), 7.62 (dd, 1H, J=11.86, 1.77 Hz), 7.7 (t, 2H, J=9 Hz), 1.7 (s, 6H); MS (APCI) m/z 324 ([M+H]+, 100%); Anal. Calc. For C16H12F2NO2 0.5 H2O C, 57.76, H, 3.94, N, 4.21. Found: C, 57.49, H, 3.69, N, 4.03.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washThe organic layer was washed twice with aqueous ammonium chloride (100 mL) and once with brine (100 mL)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified via chromatography (silica gel, 25% ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-f96576af998b4e738a2a03fd7ec83cb1
출처 데이터셋
uspto-grants-2003_01
특허 번호
US06509334B1

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