Veratrole → N-Boc-(2,3-dimethoxyphenyl)-4-piperidinylmethanone

HRID 51274ノート

反応式

HRID 51274 の反応式
[C:1]1([O:9][CH3:10])[C:2](=[CH:5][CH:6]=[CH:7][CH:8]=1)[O:3][CH3:4].C([Li])CCC.COCN[C:20]([CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1)=[O:21]>O1CCCC1>[CH3:4][O:3][C:2]1[C:1]([O:9][CH3:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C:20]([CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1)=[O:21]

参加物

5

反応物 3

HCID 7043Veratrole2 回HCID 442032024-(Methoxymethylcarbamoyl)piperidine-1-carboxylic acid tert-butyl esterHCID 178418339Butyllithium

生成物 1

HCID 46780868N-Boc-(2,3-dimethoxyphenyl)-4-piperidinylmethanone

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

A suitable reactor maintained under nitrogen is charged with veratrole (12.5 kg, 90.0 mol) and about 87 kg of tetrahydrofuran. The solution is cooled and maintained below −10° C. while adding n-butyl lithium (22.9 kg, 83.3 mol, 23.3% solution in hexane). The mixture is warmed to about 0° C. for 1 hour, then to about 25° C. for at least 2 hours. In a separate reactor maintained under nitrogen is charged with 4-[(methoxymethylamino)carbonyl]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester (15) as a heptanes wet cake (15.6 kg, 57.3 mol, dry weight basis) and about 66 kg of tetrahydrofuran. The mixture is cooled below −10° C.1 and the lithiated veratrole solution is added at such a rate to maintain the temperature below −10° C. The mixture is warmed to about 25° C. for at least 6 hours.2 When complete, the title compound may be utilized in Scheme H, step a, Example 108 as the reaction solution.

後処理

  1. temperatureA suitable reactor maintained under nitrogen
  2. temperatureThe solution is cooled
  3. temperaturemaintained below −10° C.
  4. waitto about 25° C. for at least 2 hours
  5. temperatureIn a separate reactor maintained under nitrogen
  6. temperatureThe mixture is cooled below −10° C
  7. temperatureto maintain the temperature below −10° C
  8. temperatureThe mixture is warmed to about 25° C. for at least 6 hours

出典と根拠

ORDレコード
ord-8c2dc7abec23425880c06c4a583ab511
出典データセット
uspto-grants-2004_03
特許番号
US06713627B2

反応ノート

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