tert-Butanol → N-(t-butoxycarbonylsulfamoyl)-N-(2-benzyloxy-6-fluorophenyl)glycine methyl ester

HRID 889272Notes

Reaction equation

HRID 889272 reaction equation
Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].[C:8]([OH:12])([CH3:11])([CH3:10])[CH3:9].[CH2:13]([O:20][C:21]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:22]=1[NH:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CCN(C(C)C)C(C)C>ClCCl>[CH3:28][O:27][C:25](=[O:26])[CH2:24][N:23]([S:2](=[O:4])(=[O:3])[NH:5][C:6]([O:12][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:7])[C:22]1[C:29]([F:33])=[CH:30][CH:31]=[CH:32][C:21]=1[O:20][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 70918Chlorosulfonyl isocyanateHCID 81531DiisopropylethylamineHCID 68430918Methyl 2-(2-benzyloxy-6-fluoroanilino)-acetate

Product 1

HCID 68429517N-(t-butoxycarbonylsulfamoyl)-N-(2-benzyloxy-6-fluorophenyl)glycine methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Chlorosulfonylisocyanate (379 μL, 616 mg, 4.36 mmol) is dissolved in dichloromethane (5 mL) cooled in an ice bath. To this is added a solution of tert.-butanol (416 μL, 322 mg, 4.35 mmol) in dichloromethane (2 mL) dropwise then the mixture is stirred cold for 5 min then 15 min at RT. To the rechilled solution is added dropwise a solution of methyl 2-(2-benzyloxy-6-fluoroanilino)-acetate (840 mg, 2.90 mmol) and Hunig's base (859 μL, 637 mg, 4.93 mmol) in dichloromethane and the resulting solution allowed to warm to RT. After 4 h LC/MS showed the reaction to be complete. The solution is extracted with water, and the organic layer dried, filtered, and solvent removed under reduced pressure. The residual material is chromatographed on an Isco Companion (80 g silica gel, 20-50% gradient of hexane/ethyl acetate) to afford N-(t-butoxycarbonylsulfamoyl)-N-(2-benzyloxy-6-fluorophenyl)glycine methyl ester as an oil. MS (M−1)−=467; NMR (CDCl3): δ 7.51 (br s, 1H), 7.40 (m, 5H), 7.24 (m, 2H), 6.78 (m, 2H), 5.16 (s, 2H), 4.60 (dd, J=101 and 18 Hz, 2H), 3.64 (s, 3H), 1.46 (s, 9H).

Workup

  1. temperaturecooled in an ice bath
  2. custom15 min
  3. customat RT
  4. waitAfter 4 h LC/MS showed
  5. customthe reaction
  6. extractionThe solution is extracted with water
  7. customthe organic layer dried
  8. filtrationfiltered
  9. customsolvent removed under reduced pressure
  10. customThe residual material is chromatographed on an Isco Companion (80 g silica gel, 20-50% gradient of hexane/ethyl acetate)

Sources & evidence

ORD record
ord-d50bcf1b15da4f25802579f84fe87f7c
Source dataset
uspto-grants-2012_08
Patent number
US08252820B2

Reaction notes

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