Diisopropylethylamine → Tert-butyl 4-(2-chloro-6-(3,3-difluoropyrrolidin-1-yl)pyridin-4-yl)piperidine-1-carboxylate

HRID 1057043노트

반응식

HRID 1057043 반응식
Cl.[F:2][C:3]1([F:9])[CH:8]=C[CH:6]=[N:5][CH2:4]1.Cl[C:11]1[CH:16]=[C:15]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[CH:14]=[C:13]([Cl:30])[N:12]=1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O.C(OCC)(=O)C>[Cl:30][C:13]1[CH:14]=[C:15]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[CH:16]=[C:11]([N:5]2[CH2:6][CH2:8][C:3]([F:2])([F:9])[CH2:4]2)[N:12]=1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 900150733,3-Difluoropyridine hydrochlorideHCID 90015259Tert-butyl 4-(2,6-dichloropyridin-4-yl)piperidine-1-carboxylate

생성물 1

HCID 90067487Tert-butyl 4-(2-chloro-6-(3,3-difluoropyrrolidin-1-yl)pyridin-4-yl)piperidine-1-carboxylate수율 47%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

A solution of 3,3-difluoropyridine hydrochloride (533 mg, 3.72 mmol, 3.18 equiv), tert-butyl 4-(2,6-dichloropyridin-4-yl)piperidine-1-carboxylate (1.00 g, 1.17 mmol, 1 equiv), and N,N-diisopropylethylamine (1.23 mL, 7.03 mmol, 6.00 equiv) in N-methylpyrrolidinone (2.3 mL) was heated at 130° C. in the microwave (CEM) for 1.5 h. The reaction mixture was diluted with ethyl acetate (50 mL), and the resulting solution was washed with saturated aqueous ammonium chloride solution (2×20 mL). The aqueous washes were extracted with ethyl acetate (25 mL). The combined organic was washed with water (25 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by flash column chromatography (4:1 heptane/ethyl acetate) provided product as a clear oil (220 mg, 47% yield). 1H NMR (400 MHz, CDCl3): 6.51 (s, 1H), 6.03 (s, 1H), 4.25 (m, 2H), 3.83 (t, J=13.1 Hz, 2H), 3.67 (t, J=7.3 Hz, 2H), 2.77 (m, 2H), 2.42-2.58 (m, 3H), 1.78 (m, 2H), 1.53-1.62 (m, 2H), 1.48 (s, 9H).

후처리

  1. washthe resulting solution was washed with saturated aqueous ammonium chloride solution (2×20 mL)
  2. extractionThe aqueous washes were extracted with ethyl acetate (25 mL)
  3. washThe combined organic was washed with water (25 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash column chromatography (4:1 heptane/ethyl acetate)

출처 및 근거

ORD 기록
ord-654f6b5618ac4a579209a2c660adf643
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09399636B2

반응 노트

불러오는 중…