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

HRID 1963214노트

반응식

HRID 1963214 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매2회HCID 6342Acetonitrile용매

실험 절차

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)+

후처리

  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

출처 및 근거

ORD 기록
ord-592d55a8015b4d2ca3e491fa99408042
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415378B2

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