tert-butyl 1-tosyl-1H-pyrrole-3-carboxylate → tert-butyl 2-((R)-1-((S)-1,1-dimethylethylsulfinamido)ethyl)-1-tosyl-1H-pyrrole-3-carboxylate

HRID 1056142ノート

反応式

HRID 1056142 の反応式
[S:1]([N:11]1[CH:15]=[CH:14][C:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[CH:23](=[N:25]/[S@:26]([C:28]([CH3:31])([CH3:30])[CH3:29])=[O:27])\[CH3:24]>C1COCC1>[CH3:29][C:28]([CH3:31])([S@@:26]([NH:25][C@@H:23]([C:12]1[N:11]([S:1]([C:4]2[CH:5]=[CH:6][C:7]([CH3:8])=[CH:9][CH:10]=2)(=[O:2])=[O:3])[CH:15]=[CH:14][C:13]=1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH3:24])=[O:27])[CH3:30]

参加物

4

反応物 2

HCID 67965365tert-butyl 1-tosyl-1H-pyrrole-3-carboxylateHCID 77058989(S)-N-[(1E)-ethylidene]-2-methylpropane-2-sulfinamide

生成物 1

HCID 89783858tert-butyl 2-((R)-1-((S)-1,1-dimethylethylsulfinamido)ethyl)-1-tosyl-1H-pyrrole-3-carboxylate収率 43.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of tert-butyl 1-tosyl-1H-pyrrole-3-carboxylate (,287a 1.67 g, 5.20 mmol) in 40 mL of THF at −78° C. was added LDA(Aldrich) (1.7 M solution in heptane/THF/ethylbenzene, 3.67 mL, 6.24 mmol) slowly dropwise. After 45 min, a solution of (S,E)-N-ethylidene-2-methylpropane-2-sulfinamide (Prepared according to PCT Int. Appl., WO2005103020; 0.765 g, 5.20 mmol) in THF was added slowly dropwise via syringe over several min. After 15 min, the acetone/dry ice bath was removed and the reaction was quenched by dropwise addition of saturated aq. NH4Cl and Et2O. The organic layer was washed with saturated aq. NH4Cl once, saturated aq. NaCl once and the organics were dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography (80 g ISCO redisep gold column) using 0-50% EtOAc/hexanes. The product-containing fractions were concentrated to afford tert-butyl 2-((R)-1-((S)-1,1-dimethylethylsulfinamido)ethyl)-1-tosyl-1H-pyrrole-3-carboxylate (287b; 1.05 g, 2.24 mmol, 43% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.73 (2H, d, J=8.2 Hz), 7.28-7.34 (3H, m), 6.58 (1H, d, J=3.3 Hz), 5.95 (1H, d, J=9.2 Hz), 5.14 (1H, br. s.), 2.43 (3H, s), 1.50-1.54 (12H, m), 0.96 (9H, s). m/z (ESI, +ve) 469.1 (MA-1)11.

後処理

  1. waitAfter 15 min
  2. customthe acetone/dry ice bath was removed
  3. customthe reaction was quenched by dropwise addition of saturated aq. NH4Cl and Et2O
  4. washThe organic layer was washed with saturated aq. NH4Cl once
  5. dry with materialsaturated aq. NaCl once and the organics were dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. additionThe material was treated with DCM
  9. custompurified by silica gel chromatography (80 g ISCO redisep gold column)
  10. concentrationThe product-containing fractions were concentrated

出典と根拠

ORDレコード
ord-3787c7e35b674e0faadd6bca0c0e5ca0
出典データセット
uspto-grants-2016_07
特許番号
US09394297B2

反応ノート

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