Hydrochloric Acid → 4-Methyl-6-trifluoromethyl-3,4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid

HRID 1697456노트

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HRID 1697456 반응식
C([O:3][C:4]([CH:6]1[CH2:11][NH:10][C:9]2[CH:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:8]=2[O:7]1)=[O:5])C.[C:20]([O-])([O-])=O.[K+].[K+].IC.Cl>CN(C=O)C.O>[CH3:20][N:10]1[C:9]2[CH:12]=[C:13]([C:16]([F:17])([F:18])[F:19])[CH:14]=[CH:15][C:8]=2[O:7][CH:6]([C:4]([OH:3])=[O:5])[CH2:11]1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 11747775ethyl 6-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate

생성물 1

HCID 581186544-Methyl-6-trifluoromethyl-3,4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid수율 14.4%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
150 °C

실험 절차

To a solution of 6-trifluoromethyl-3,4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid ethyl ester (650 mg, 2.4 mmol) in anhydrous DMF (7 mL) was added K2CO3 (816 mg, 5.9 mmol), followed by iodomethane (294 μL, 4.7 mmol). The reaction was heated in the microwave (300 W, 150° C.) for 1 hour. After cooling, the mixture was poured into water (50 mL), acidified with 2N HCl and extracted with EtOAc (3×50 mL). The combined organics were washed with brine (3×50 mL), dried (MgSO4), filtered and concentrated. Flash chromatography (0 to 12% MeOH in DCM) gave the title compound (90 mg, 10%) as a beige solid. m/z=262.1 (M+1), r.t.=3.28 mins. 1H NMR (400 MHz; d6-DMSO) δ 6.93-6.86 (3H, m), 4.85 (1H, s), 3.45-3.36 (2H, m), 2.86 (3H, s).

후처리

  1. temperatureAfter cooling
  2. extractionextracted with EtOAc (3×50 mL)
  3. washThe combined organics were washed with brine (3×50 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-ad9aa6d9e32d40959cfc95b15a9781c8
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163901B2

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