Triethylamine → 2-(2,6-Difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

HRID 1963316ノート

反応式

HRID 1963316 の反応式
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][CH:5]1[CH2:10][CH:9]([C:11]([O:13]C)=[O:12])[CH2:8][CH2:7][N:6]1[C:15]([O:17][CH3:18])=[O:16].[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][CH:5]1[CH2:10][CH:9]([C:11]([OH:13])=[O:12])[CH2:8][CH2:7][N:6]1[C:15]([O:17][CH3:18])=[O:16]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66734964Dimethyl 2-(2,6-difluorobenzyl)piperidine-1,4-dicarboxylate

生成物 1

HCID 667316802-(2,6-Difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid収率 82.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 6342Acetonitrile溶媒

実験手順

Dimethyl 2-(2,6-difluorobenzyl)piperidine-1,4-dicarboxylate (5.98 g, 18.27 mmol) was dissolved in acetonitrile (50 mL) and water (1 mL), then lithium bromide (12.69 g, 146.16 mmol) and triethylamine (10.13 mL, 73.08 mmol) were added. The suspension was heated to reflux for 3.5 h, then water (60 mL) and MTBE (180 mL) were added. The organic phase was extracted with water (×2). The combined water phases were acidified to pH 1 with 3.8 M HCl and extracted with MTBE (×2). The combined organic phases were washed with water, dried with MgSO4, filtered through celite and concentrated to give 2-(2,6-difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (4.72 g, 82%) as a light yellow solid. MS m/z 314 (M+H)+

後処理

  1. temperatureThe suspension was heated
  2. temperatureto reflux for 3.5 h
  3. extractionThe organic phase was extracted with water (×2)
  4. extractionextracted with MTBE (×2)
  5. washThe combined organic phases were washed with water
  6. dry with materialdried with MgSO4
  7. filtrationfiltered through celite and
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-f1aa74f13a2c4286a482d944903eb5c4
出典データセット
uspto-grants-2013_04
特許番号
US08415378B2

反応ノート

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