L-Proline 1,1-dimethylethyl ester → (S)-tert-Butyl-1-(2-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)-2-oxoethyl)pyrrolidine-2-carboxylate

HRID 424527ノート

反応式

HRID 424527 の反応式
Cl[CH2:2][C:3]([N:5]1[CH2:10][CH2:9][S:8][C:7]2[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:6]1=2)=[O:4].[NH:18]1[CH2:22][CH2:21][CH2:20][C@H:19]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]>C1COCC1.CCOC(C)=O.C(=O)(O)[O-].[Na+]>[C:26]([O:25][C:23]([C@@H:19]1[CH2:20][CH2:21][CH2:22][N:18]1[CH2:2][C:3]([N:5]1[CH2:10][CH2:9][S:8][C:7]2[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:6]1=2)=[O:4])=[O:24])([CH3:29])([CH3:27])[CH3:28]

参加物

6

反応物 2

HCID 6453108L-Proline 1,1-dimethylethyl esterHCID 591440782-Chloro-1-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethanone

生成物 1

HCID 59144152(S)-tert-Butyl-1-(2-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)-2-oxoethyl)pyrrolidine-2-carboxylate

試薬・触媒・溶媒 3

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒HCID 516892Sodium Bicarbonate溶媒2 回

反応条件

温度
55 °C

実験手順

A solution of 2-chloro-1-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethanone (1.0 g, 3.67 mmol) in THF (20 mL) was treated with (S)-tert-butyl pyrrolidine-2-carboxylate (0.942 g, 5.50 mmol), followed by saturated sodium bicarbonate (4 mL). The mixture was heated at 55° C. for 3 hours then stirred at room temperature overnight (17 hours). The mixture was diluted with EtOAc (50 mL) and saturated sodium bicarbonate (10 mL) then stirred for 20 minutes. The contents were poured into a separatory funnel, and the organic layer was separated, dried (Na2SO4), filtered, and concentrated to give a dark yellow residue. This residue was subjected to silica gel chromatography using the Biotage purification system (column: Silicycle 40 g; 20:80 EtOAc:hexanes gradient to 60:40 EtOAc:hexanes over 8 column volumes; flow rate: 35 mL/min; collection wavelength: 254 nm). A yellow residue was obtained (1.47 g, 98%). 1H-NMR (CDCl3) δ 8.09 (d, J=2.4 Hz, 1H), 7.91 (dd, J=2.4, 8.7 Hz, 1H), 7.75 (d, J=9.0 Hz, 1H), 4.10 (brs, 2H), 3.74 (brd, J=13.2 Hz, 1H), 3.40 (brd, J=13.5 Hz, 1H), 3.37-3.21 (m, 3H), 3.12-3.04 (m, 1H), 2.61 (brdd, J=8.1, 16.2 Hz, 1H), 2.21-2.07 (m, 1H), 1.95-1.77 (m, 3H), 1.43 (s, 9H); ESI-MS (m/z, %): 408 (MH+, 50), 352 (100).

後処理

  1. stirringthen stirred for 20 minutes
  2. additionThe contents were poured into a separatory funnel
  3. customthe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a dark yellow residue
  8. customthe Biotage purification system (column: Silicycle 40 g; 20:80 EtOAc:hexanes gradient to 60:40 EtOAc:hexanes over 8 column volumes; flow rate: 35 mL/min; collection wavelength: 254 nm)
  9. customA yellow residue was obtained (1.47 g, 98%)

出典と根拠

ORDレコード
ord-f7205af8d7c043ec8838b20f97d26561
出典データセット
uspto-grants-2012_01
特許番号
US08106043B2

反応ノート

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