Dichloromethane → (S)-N-benzyl-2-(4-hydroxy-2-oxopyrrolidin-1-yl)-4-methylthiazole-5-carboxamide

HRID 883170ノート

反応式

HRID 883170 の反応式
O=C1CC([O:8][C@@H:9]2[CH2:13][NH:12][C:11](=[O:14])[CH2:10]2)CCO1.[CH2:15]([NH:22][C:23]([C:25]1[S:29][C:28](Br)=[N:27][C:26]=1[CH3:31])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>C1(C)C=CC=CC=1.C(OCC)(=O)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:15]([NH:22][C:23]([C:25]1[S:29][C:28]([N:12]2[CH2:13][C@@H:9]([OH:8])[CH2:10][C:11]2=[O:14])=[N:27][C:26]=1[CH3:31])=[O:24])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 579593962-Bromo-4-methyl-thiazole-5-carboxylic acid benzylamideHCID 68495162(4S)-4-(2-oxotetrahydro-2H-pyran-4-yloxy)pyrrolidin-2-one

生成物 1

HCID 24801838(S)-N-benzyl-2-(4-hydroxy-2-oxopyrrolidin-1-yl)-4-methylthiazole-5-carboxamide収率 53%

試薬・触媒・溶媒 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

A mixture of (4S)-4-(2-oxotetrahydro-2H-pyran-4-yloxy)pyrrolidin-2-one (0.036 g, 0.19 mmol), N-benzyl-2-bromo-4-methylthiazole-5-carboxamide (0.050 g, 0.16 mmol), cesium carbonate (0.079 g, 0.24 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (0.003 g, 0.003 mmol) and xantphos (0.004 g, 0.006 mmol) in anhydrous toluene (3 mL) was subjected to microwave irradiation at 80° C. for 20 min. The reaction mixture was diluted with ethyl acetate (10 mL) and washed with water (4 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in ethanol and a catalytic amount of pyridinium p-toluenesulfonate was added to the solution. The reaction mixture was heated at 50° C. for 6 hours and concentrated in vacuo. The residue was dissolved in dichloromethane (15 mL) and washed with water (5 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The obtained white solid was washed with diethyl ether (25 mL) and dried in air to afford the title compound (0.028 g, 53%): mp 203-204° C. (diethyl ether); 1H NMR (300 MHz, DMSO-d6) δ 8.60 (t, J=6.0 Hz, 1H), 7.33-7.17 (m, 5H), 5.46 (d, J=3.8 Hz, 1H), 4.47-4.41 (m, 1H), 4.35 (d, J=6.0 Hz, 2H), 4.12-4.04 (m, 1H), 3.93-3.85 (m, 1H), 3.00-2.90 (m, 1H), 2.48 (s, 3H), 2.42-2.33 (m, 1H); 13C NMR (75 MHz, DMSO-d6) δ 173.3, 162.1, 155.9, 140.0, 128.7, 127.7, 127.2, 119.4, 63.6, 57.0, 43.1, 41.7, 17.5; MS (ES+) m/z 332.2 (M+1).

後処理

  1. customirradiation at 80° C. for 20 min
  2. washwashed with water (4 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in ethanol
  7. additiona catalytic amount of pyridinium p-toluenesulfonate was added to the solution
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in dichloromethane (15 mL)
  10. washwashed with water (5 mL)
  11. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. washThe obtained white solid was washed with diethyl ether (25 mL)
  15. customdried in air

出典と根拠

ORDレコード
ord-990c3c50656042f8aa410aad2d8bb536
出典データセット
uspto-grants-2012_08
特許番号
US08236835B2

反応ノート

読み込み中…