Sodium hydride → benzyl 4-((1R,2S)-2-(2-(5-(methylsulfonyl)pyridin-2-yloxy)ethyl)cyclopropyl)piperidine-1-carboxylate

HRID 1850712ノート

反応式

HRID 1850712 の反応式
[H-].[Na+].[OH:3][CH2:4][CH2:5][C@@H:6]1[CH2:8][C@@H:7]1[CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:11][CH2:10]1.Br[C:26]1[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][N:27]=1>CN(C)C=O.C(OCC)(=O)C.O>[CH3:35][S:32]([C:29]1[CH:30]=[CH:31][C:26]([O:3][CH2:4][CH2:5][C@@H:6]2[CH2:8][C@@H:7]2[CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[O:16])[CH2:11][CH2:10]2)=[N:27][CH:28]=1)(=[O:34])=[O:33]

参加物

7

反応物 3

HCID 24758Sodium hydrideHCID 98994832-Bromo-5-(methylsulfonyl)pyridineHCID 70856295Benzyl 4-((1R,2S)-2-(2-hydroxyethyl)cyclopropyl)piperidine-1-carboxylate

生成物 1

HCID 70819038benzyl 4-((1R,2S)-2-(2-(5-(methylsulfonyl)pyridin-2-yloxy)ethyl)cyclopropyl)piperidine-1-carboxylate

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Sodium hydride (424 mg, 60% dispersion in mineral oil, 10.6 mmol) was added to a solution of benzyl 4-((1R,2S)-2-(2-hydroxyethyl)cyclopropyl)piperidine-1-carboxylate (1.07 g, 3.53 mmol) in N,N-dimethylformamide (10 mL) under nitrogen at RT. The mixture was stirred for 30 min at RT and 2-bromo-5-(methylsulfonyl)pyridine (1.25 g, 5.30 mmol) was added. The mixture was stirred overnight, diluted with ethyl acetate (100 mL) and water (50 mL), and the layers were separated. The organic layer was washed with brine (2×25 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (40 g RediSep, eluted with a gradient of hexanes to ethyl acetate, 9:1, 200 mL; 4:1, 500 mL; 1:1, 1 L) to provide the title compound as a light yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.71 (dd, J=0.5, 2.5 Hz, 1H), 8.03 (dd, J=2.5, 8.7 Hz, 1H), 7.40-7.28 (m, 5H), 6.84 (dd, J=0.6, 8.7 Hz, 1H), 5.13 (s, 2H), 4.48 (t, J=7.2 Hz, 2H), 4.30-4.10 (m, 2H), 3.07 (s, 3H), 2.90-2.60 (m, 2H), 2.20-2.00 (m, 1H), 1.85-1.65 (m, 2H), 1.60-1.45 (m, 1H), 1.45-1.20 (m, 2H), 1.10-0.85 (m, 2H), 0.75-0.50 (m, 2H), −0.12 (q, J=5.1 Hz, 1H). MS (Multimode) m/z 459 [M+H]+.

後処理

  1. stirringThe mixture was stirred overnight
  2. customthe layers were separated
  3. washThe organic layer was washed with brine (2×25 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (40 g RediSep
  8. washeluted with a gradient of hexanes to ethyl acetate, 9:1, 200 mL

出典と根拠

ORDレコード
ord-3bca511455b6452d8a20609238a91537
出典データセット
uspto-grants-2015_02
特許番号
US08957062B2

反応ノート

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