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 1056142Notes

Reaction equation

HRID 1056142 reaction equation
[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]

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-3787c7e35b674e0faadd6bca0c0e5ca0
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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