Benzoic acid, 3-(chlorosulfonyl)-, methyl ester → 3-[(1-tert-Butoxycarbonyl-cyclobutylmethyl)-sulfamoyl]-benzoic acid methyl ester

HRID 2170108Notes

Reaction equation

HRID 2170108 reaction equation
[C:1]([O:5][C:6]([C:8]1([CH2:12][NH2:13])[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[S:15]([C:18]1[CH:19]=[C:20]([CH:25]=[CH:26][CH:27]=1)[C:21]([O:23][CH3:24])=[O:22])(=[O:17])=[O:16]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:24][O:23][C:21](=[O:22])[C:20]1[CH:25]=[CH:26][CH:27]=[C:18]([S:15](=[O:16])(=[O:17])[NH:13][CH2:12][C:8]2([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10][CH2:11]2)[CH:19]=1

Participants

5

Reactant 2

HCID 113339Benzoic acid, 3-(chlorosulfonyl)-, methyl esterHCID 667975881366068-12-3

Product 1

HCID 667975353-[(1-tert-Butoxycarbonyl-cyclobutylmethyl)-sulfamoyl]-benzoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 1-aminomethyl-cyclobutanecarboxylic acid tert-butyl ester (step 2) (1.47 g, 7.38 mmol) in DCM (40 ml) was treated with TEA (2.57 ml, 18.44 mmol) followed by methyl 3-(chlorosulfonyl)benzoate (1.91 g, 8.11 mmol) and DMAP (0.09 g, 0.74 mmol). The mixture was stirred at RT for 2 h and then partitioned between DCM and water. The aqueous portion was extracted with DCM and the combined organic extracts were washed with 0.1N HCl, brine, dried over MgSO4 and concentrated in vacuo. Purification of the resulting oil by chromatography on silica eluting with 0-40% EtOAc in iso-hexane afforded the title compound as a colourless oil; 1H NMR (400 MHz, CDCl3) δ 8.56 (1H, s), 8.27 (1H, d), 8.08 (1H, d), 7.64 (1H, t), 5.21 (1H, br t), 3.98 (3H, s), 3.20 (2H, d), 2.37 (2H, m), 1.96 (4H, m), 1.46 (9H, s).

Workup

  1. custompartitioned between DCM and water
  2. extractionThe aqueous portion was extracted with DCM
  3. washthe combined organic extracts were washed with 0.1N HCl, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the resulting oil by chromatography on silica eluting with 0-40% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-b26b822d8ec24513bf7cbe0274169b48
Source dataset
uspto-grants-2015_06
Patent number
US09050339B2

Reaction notes

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