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

HRID 1057043ノート

反応式

HRID 1057043 の反応式
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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-654f6b5618ac4a579209a2c660adf643
出典データセット
uspto-grants-2016_07
特許番号
US09399636B2

反応ノート

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