Toluene → tert-butyl 1-tosyl-1H-pyrrole-3-carboxylate

HRID 1056141Notes

Reaction equation

HRID 1056141 reaction equation
[S:1]([N:11]1[CH:15]=[CH:14][C:13]([C:16]([OH:18])=[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].[C:19]1([CH3:25])[CH:24]=CC=C[CH:20]=1.C(OC(OC(C)(C)C)N(C)C)(C)(C)C>O>[S:1]([N:11]1[CH:15]=[CH:14][C:13]([C:16]([O:18][C:19]([CH3:25])([CH3:24])[CH3:20])=[O:17])=[CH:12]1)([C:4]1[CH:5]=[CH:6][C:7]([CH3:8])=[CH:9][CH:10]=1)(=[O:2])=[O:3]

Participants

5

Reactant 3

HCID 1140TolueneHCID 5477121,1-bis(1,1-dimethylethoxy)-N,N,N-trimethylamineHCID 27246931-(4-methylbenzenesulfonyl)-1H-pyrrole-3-carboxylic acid

Product 1

HCID 67965365tert-butyl 1-tosyl-1H-pyrrole-3-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 3-neck RBF was charged with 1-tosyl-1H-pyrrole-3-carboxylic acid (Astatech, Bristol, Pa.; 2.00 g, 7.54 mmol) and 20 mL anhydrous toluene, and was fitted with a water cooled reflux condenser and heated to reflux under N2. N,N-dimethylformamide di-tert-butyl acetal (Aldrich; 14.46 mL, 60.4 mmol) was added slowly dropwise via addition funnel. The reaction mixture was stirred for 1 h, then the oil bath was turned off, and the reaction mixture was cooled to RT over the weekend. It was partitioned between saturated aq. NaHCO3 and Et2O. The organic layer was washed with saturated aq. NaHCO3 once, saturated aq. NaCl once, and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography (80 g column) using 0-20% EtOAc/hexanes. The product-containing fractions were concentrated to afford tert-butyl 1-tosyl-1H-pyrrole-3-carboxylate (287a; 2.22 g, 6.91 mmol, 92% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.80 (2H, d, J=8.4 Hz), 7.63-7.70 (1H, m), 7.33 (2H, d, J=8.2 Hz), 7.09 (1H, dd, J=3.3, 2.3 Hz), 6.61 (1H, dd, J=3.3, 1.6 Hz), 2.43 (3H, s), 1.53 (9H, s). m/z (ESI, +ve) 266.0 (M+H)+.

Workup

  1. temperaturecooled
  2. temperaturereflux condenser
  3. temperatureheated
  4. temperatureto reflux under N2
  5. customIt was partitioned between saturated aq. NaHCO3 and Et2O
  6. washThe organic layer was washed with saturated aq. NaHCO3 once
  7. dry with materialsaturated aq. NaCl once, and the organics were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. additionThe material was treated with DCM
  11. custompurified by silica gel chromatography (80 g column)
  12. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-69d034fef01d4eb085ecd7e62644e851
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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