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

HRID 1697456ノート

反応式

HRID 1697456 の反応式
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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
150 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-ad9aa6d9e32d40959cfc95b15a9781c8
出典データセット
uspto-grants-2012_04
特許番号
US08163901B2

反応ノート

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