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

HRID 1963316노트

반응식

HRID 1963316 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매2회HCID 6342Acetonitrile용매

실험 절차

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)+

후처리

  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

출처 및 근거

ORD 기록
ord-f1aa74f13a2c4286a482d944903eb5c4
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415378B2

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