4-Toluenesulfonyl chloride → Toluene-4-sulfonic acid 4-isopropoxy-6-(1-methyl-1H-pyrazol-3-ylcarbamoyl)-2,3-dihydro-benzofuran-2-ylmethyl ester

HRID 1177212Notes

Reaction equation

HRID 1177212 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8]([C:10]2[CH:20]=[C:19]([O:21][CH:22]([CH3:24])[CH3:23])[C:13]3[CH2:14][CH:15]([CH2:17][OH:18])[O:16][C:12]=3[CH:11]=2)=[O:9])=[N:3]1.[C:25]1([CH3:35])[CH:30]=[CH:29][C:28]([S:31](Cl)(=[O:33])=[O:32])=[CH:27][CH:26]=1>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[CH:22]([O:21][C:19]1[C:13]2[CH2:14][CH:15]([CH2:17][O:18][S:31]([C:28]3[CH:29]=[CH:30][C:25]([CH3:35])=[CH:26][CH:27]=3)(=[O:33])=[O:32])[O:16][C:12]=2[CH:11]=[C:10]([C:8](=[O:9])[NH:7][C:4]2[CH:5]=[CH:6][N:2]([CH3:1])[N:3]=2)[CH:20]=1)([CH3:24])[CH3:23]

Participants

5

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 595598442-Hydroxymethyl-4-isopropoxy-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

Product 1

HCID 59560417Toluene-4-sulfonic acid 4-isopropoxy-6-(1-methyl-1H-pyrazol-3-ylcarbamoyl)-2,3-dihydro-benzofuran-2-ylmethyl esterYield 78.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

To a solution of 2-hydroxymethyl-4-isopropoxy-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (215) (506 mg, 1.530 mmol) in pyridine (10 mL) was added DMAP (20 mg), followed by p-toluenesulfonyl chloride (533 mg, 2.79 mmol). The mixture was stirred at room temperature overnight. The reaction was quenched with water, extracted with 3× EtOAc, dried over Na2SO4, concentrated and purified by flash column chromatography with 35-60% EtOAc in hexanes to give a white solid (580 mg, 78% yield). 1H NMR (400 MHz, CDCl3) δ 8.38 (s, 1 H) 7.78 (d, J=8.34 Hz, 2 H) 7.35 (d, J=8.08 Hz, 2 H) 7.29 (d, J=2.27 Hz, 1 H) 6.96 (s, 1 H) 6.80 (d, J=2.27 Hz, 1 H) 6.69 (d, J=1.26 Hz, 1 H) 5.01 (dd, J=4.93, 1.89 Hz, 1 H) 4.56-4.66 (m, 1 H) 4.19 (dd, J=5.05, 2.27 Hz, 2 H) 3.81 (s, 3 H) 3.24 (dd, J=16.55, 9.73 Hz, 1 H) 2.95 (dd, J=16.42, 6.82 Hz, 1 H) 2.45 (s, 3 H) 1.30-1.35 (m, 6 H); LCMS for C24H27N3O6S m/z 486.20 (M+H+).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with 3× EtOAc
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. custompurified by flash column chromatography with 35-60% EtOAc in hexanes

Sources & evidence

ORD record
ord-d3c46fff2a7546d18cc87133b81adbcc
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

Loading…