Triethylamine → 2-(3,5-Difluoro-4-(trifluoromethyl)phenyl)-1-(methoxy-carbonyl)piperidine-4-carboxylic acid

HRID 1963214ノート

反応式

HRID 1963214 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH:13]2[CH2:18][CH:17]([C:19]([O:21]C)=[O:20])[CH2:16][CH2:15][N:14]2[C:23]([O:25][CH3:26])=[O:24])[CH:5]=[C:6]([F:12])[C:7]=1[C:8]([F:11])([F:10])[F:9].[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[F:12][C:6]1[CH:5]=[C:4]([CH:13]2[CH2:18][CH:17]([C:19]([OH:21])=[O:20])[CH2:16][CH2:15][N:14]2[C:23]([O:25][CH3:26])=[O:24])[CH:3]=[C:2]([F:1])[C:7]=1[C:8]([F:9])([F:11])[F:10]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66732303Dimethyl 2-(3,5-difluoro-4-(trifluoromethyl)phenyl)-piperidine-1,4-dicarboxylate

生成物 1

HCID 667321922-(3,5-Difluoro-4-(trifluoromethyl)phenyl)-1-(methoxy-carbonyl)piperidine-4-carboxylic acid収率 86%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 6342Acetonitrile溶媒

実験手順

Dimethyl 2-(3,5-difluoro-4-(trifluoromethyl)phenyl)piperidine-1,4-dicarboxylate (2.851 g, 7.48 mmol) was dissolved in acetonitrile (25 mL) and water (2.5 mL), then lithium bromide (5.19 g, 59.82 mmol) was added followed by triethylamine (4.15 mL, 29.91 mmol). The reaction mixture was heated under reflux for 1 h. MTBE (150 mL) and water (150 mL) were added, shaken and the phases separated. The organic phase was extracted with water (2×150 mL). The combined aqueous phases were acidified with 3 M HCl to pH 1 and extracted with MTBE (2×450 mL). The combined organic phases were dried over Na2SO4, filtered and evaporated in vacuo yielding 2-(3,5-difluoro-4-(trifluoromethyl)phenyl)-1-(methoxy-carbonyl)piperidine-4-carboxylic acid (2.363 g, 86%). MS m/z 368 (M+H)+

後処理

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 1 h
  3. customthe phases separated
  4. extractionThe organic phase was extracted with water (2×150 mL)
  5. extractionextracted with MTBE (2×450 mL)
  6. dry with materialThe combined organic phases were dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated in vacuo

出典と根拠

ORDレコード
ord-592d55a8015b4d2ca3e491fa99408042
出典データセット
uspto-grants-2013_04
特許番号
US08415378B2

反応ノート

読み込み中…