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

HRID 51270

反応式

HRID 51270 の反応式
[Li]CCCC.[C:6]1([O:14][CH3:15])[C:7](=[CH:10][CH:11]=[CH:12][CH:13]=1)[O:8][CH3:9].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]>CCCCCC.O1CCCC1>[CH3:9][O:8][C:7]1[C:6]([O:14][CH3:15])=[CH:13][CH:12]=[CH:11][C:10]=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

6

反応物 3

HCID 7043VeratroleHCID 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 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8058Hexane溶媒

反応条件

温度
0 °C

実験手順

A solution of n-BuLi (2.5M, 452 mL) in hexane was added to a solution of veratrole (149 g, 1.08 mol) in anhydrous tetrahydrofuran (1.2 L) over 10 minutes at −78° C. under nitrogen. The resulting solution was stirred at 0° C. for 1 hour and room temperature for 4 hours. A solution of 4-[(methoxymethylamino)carbonyl]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester (15) (275 g, 1.01 mol) in tetrahydrofuran (800 mL) was added to the reaction slurry at −65° C. over 20 minutes. The mixture was warmed to room temperature, stirred for 18 hours and quenched with saturated ammonium chloride (1 L). After stirring for 1 hour, the phases were separated and the aqueous layer was extracted with ethyl ether (1 L). The combined organic solutions were washed with brine (2 L) and dried (MgSO4). The mixture was filtered and the filtrate was concentrated (30° C./20 torr) to a residue (413 g). The solution may be used directly in Scheme L, step a, Example 108.

後処理

  1. temperatureThe mixture was warmed to room temperature
  2. stirringstirred for 18 hours
  3. customquenched with saturated ammonium chloride (1 L)
  4. stirringAfter stirring for 1 hour
  5. customthe phases were separated
  6. extractionthe aqueous layer was extracted with ethyl ether (1 L)
  7. washThe combined organic solutions were washed with brine (2 L)
  8. dry with materialdried (MgSO4)
  9. filtrationThe mixture was filtered
  10. concentrationthe filtrate was concentrated (30° C./20 torr) to a residue (413 g)

出典と根拠

ORDレコード
ord-74e44df03d06443bac63a75ca0bbbe91
出典データセット
uspto-grants-2004_03
特許番号
US06713627B2

関連ノート

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