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

HRID 51274

반응식

HRID 51274 반응식
[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]

참가 물질

5

반응물 3

HCID 7043Veratrole2회HCID 442032024-(Methoxymethylcarbamoyl)piperidine-1-carboxylic acid tert-butyl esterHCID 178418339Butyllithium

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-8c2dc7abec23425880c06c4a583ab511
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06713627B2

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