Methanol → 2-(difluoromethoxy)-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine

HRID 597927ノート

反応式

HRID 597927 の反応式
[F:1][CH:2]([F:22])[O:3][C:4]1[CH:5]=[CH:6][C:7]2[CH:13]([CH3:14])[CH2:12][N:11](C(=O)C(F)(F)F)[CH2:10][CH2:9][C:8]=2[N:21]=1.C([O-])([O-])=O.[K+].[K+].CO>O>[F:22][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]2[CH:13]([CH3:14])[CH2:12][NH:11][CH2:10][CH2:9][C:8]=2[N:21]=1

参加物

5

反応物 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 86616698HCID 86616698、化合物

生成物 1

HCID 236539042-(difluoromethoxy)-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine収率 36%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

To a mixture of 5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol (77.0 mg, 281 μmol), K2CO3 (19.0 mg, 141 μmol) and DMF (1.4 ml) was added F2ClCCO2Na (47.0 mg, 310 μmol). The mixture was heated at 90° C. for 2 h. The reaction mixture was parted between sat. aq. NaHCO3 and EtOAc. The organic layer was dried, concentrated in vacuo and purified by means of column chromatography to give 49.0 mg (54%) of 2-(difluoromethoxy)-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. MS (ESI) m/z 325.2. A mixture of 2-(difluoromethoxy)-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (28.0 mg, 86.0 μmol), K2CO3 (30 mg), MeOH (1 ml) and H2O (200 μl) was heated to reflux for 10 min. The reaction mixture was concentrated in vacuo and the resulting residue was purified by column chromatography to yield 7.0 mg (36%) of 2-(difluoromethoxy)-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 7.46 (d, 1H), 6.66 (d, 1H), 3.09 (m, 2H), 3.40-2.90 (m, 4H), 2.74, (dd, 1H), 1.31 (d, 3H) ppm.

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 10 min
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe resulting residue was purified by column chromatography

出典と根拠

ORDレコード
ord-009c42a338a143a2b508dcc63afe4d21
出典データセット
uspto-grants-2011_03
特許番号
US07897595B2

反応ノート

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