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 424527노트

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HRID 424527 반응식
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]

참가 물질

6

반응물 2

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

생성물 1

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

시약·촉매·용매 3

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 516892Sodium Bicarbonate용매2회

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온도
55 °C

실험 절차

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).

후처리

  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%)

출처 및 근거

ORD 기록
ord-f7205af8d7c043ec8838b20f97d26561
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08106043B2

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