Hydrochloric Acid → 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylic acid methyl ester

HRID 729426

反応式

HRID 729426 の反応式
[F:1][C:2]1[C:3]([F:16])=[C:4]2[O:9][CH2:8][CH:7]([CH3:10])[NH:6][C:5]2=[C:11]([C:13]([OH:15])=[O:14])[CH:12]=1.Cl.[CH3:18]O>>[CH3:18][O:14][C:13]([C:11]1[CH:12]=[C:2]([F:1])[C:3]([F:16])=[C:4]2[O:9][CH2:8][CH:7]([CH3:10])[NH:6][C:5]=12)=[O:15]

参加物

4

反応物 3

HCID 313Hydrochloric Acid2 回HCID 887MethanolHCID 219790297,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylic acid

生成物 1

HCID 210411927,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylic acid methyl ester

実験手順

A solution of 2.1 g (9.1 mmol) of 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylic acid Example 31) in 50 mL of methanol is cooled to 0° C. and saturated with hydrogen chloride gas. The reaction is stirred at room temperature for 18 hours, recooled to 0° C. and resaturated with hydrogen chloride gas. After stirring an additional 24 hours at room temperature, the solvent is removed in vacuo and the residue is partitioned between dichloromethane/5% aqueous sodium bicarbonate (200:100 mL). The organic layer is separated, washed with 5% aqueous sodium bicarbonate, water, dried (MgSO4), filtered, and concentrated in vacuo affording 1.9 g of the title compound. 1H NMR (400 MHz, CDCl3): 7.27 (bs, 1H), 7.24 (m, 1M), 4.26 (m, 1H), 3.82 (s, 3H), 3.75 (m, 1H), 3.62 (m, 1H), 1.22 (d, 3H).

後処理

  1. customrecooled to 0° C.
  2. stirringAfter stirring an additional 24 hours at room temperature
  3. customthe solvent is removed in vacuo
  4. customthe residue is partitioned between dichloromethane/5% aqueous sodium bicarbonate (200:100 mL)
  5. customThe organic layer is separated
  6. washwashed with 5% aqueous sodium bicarbonate, water
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-09619287c00c441c8ecc25cb12e6c37d
出典データセット
uspto-grants-2009_09
特許番号
US07582627B2

関連ノート

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