Water → N-(t-butoxycarbonyl-sulfamoyl)-N-[2-(methoxycarbonylmethyl)-phenyl]-glycine t-butyl ester

HRID 1592020Notes

Reaction equation

HRID 1592020 reaction equation
Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].O.[C:9]([OH:13])([CH3:12])([CH3:11])[CH3:10].[CH3:14][O:15][C:16](=[O:33])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[NH:24][CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27]>C(Cl)Cl>[C:29]([O:28][C:26](=[O:27])[CH2:25][N:24]([S:2](=[O:4])(=[O:3])[NH:5][C:6]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH2:17][C:16]([O:15][CH3:14])=[O:33])([CH3:30])([CH3:32])[CH3:31]

Participants

6

Reactant 4

HCID 962WaterHCID 6386tert-ButanolHCID 70918Chlorosulfonyl isocyanateHCID 67139746[2-(t-Butoxycarbonylmethyl-amino)-phenyl]-acetic acid methyl ester

Product 1

HCID 67138370N-(t-butoxycarbonyl-sulfamoyl)-N-[2-(methoxycarbonylmethyl)-phenyl]-glycine t-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Chlorosulfonylisocyanate (1.42 mL, 16.4 mmol) is added to CH2Cl2 (20 mL) in a dry flask under argon balloon, and cooled with stirring in an ice/salt/water bath. t-Butanol (1.57 mL, 16.4 mmol) is added to this solution and stirred while maintaining the cooling for 1 h. Then a solution of the title C compound, [2-(t-butoxycarbonylmethyl-amino)-phenyl]-acetic acid methyl ester (3.84 g, 13.7 mmol) and TEA (5.7 mL, 41.1 mmol) in CH2Cl2 (90 mL) is rapidly cannulated into this above mentioned stirred, cooled solution. During 18 h the reaction slowly warms to RT, then concentrated and partitioned between EtOAc and 0.5N aqueous HCl (2×50 mL). The organic solution is washed with brine (25 mL), dried over anhydrous MgSO4, filtered and concentrated. The resulting residue is chromatographed on a 110 g silica gel RediSep (Isco Inc.) column with a 30 mL/min gradient elution of 10:90 (EtOAc:hexane) to 30:70 over 30 min, maintained at 30:70 for 15 min then to 50:50 over 6 min. Fractions containing product are combined and evaporated to give an oil which on standing in a high vacuum foamed to yield N-(t-butoxycarbonyl-sulfamoyl)-N-[2-(methoxycarbonylmethyl)-phenyl]-glycine t-butyl ester as a white foam: [M−1]−=457.

Workup

  1. temperaturecooled
  2. temperaturewhile maintaining the cooling for 1 h
  3. stirringthis above mentioned stirred
  4. temperaturecooled solution
  5. customDuring 18 h the reaction
  6. customslowly warms to RT
  7. concentrationconcentrated
  8. custompartitioned between EtOAc and 0.5N aqueous HCl (2×50 mL)
  9. washThe organic solution is washed with brine (25 mL)
  10. dry with materialdried over anhydrous MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe resulting residue is chromatographed on a 110 g silica gel RediSep (Isco Inc.) column with a 30 mL/min gradient elution of 10:90 (EtOAc:hexane) to 30:70 over 30 min
  14. temperaturemaintained at 30:70 for 15 min
  15. additionFractions containing product
  16. customevaporated
  17. customto give an oil which

Sources & evidence

ORD record
ord-539c2f03c0a046bc9059259ba51438b0
Source dataset
uspto-grants-2007_11
Patent number
US07291635B2

Reaction notes

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