Tetrahydrofuran → Phenyl 5-tert-butyl-2-methoxy-3-(methylsulfonamido)phenylcarbamate

HRID 1423265Notes

Reaction equation

HRID 1423265 reaction equation
[NH2:1][C:2]1[C:3]([O:17][CH3:18])=[C:4]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH:5]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:7]=1.C([O-])(O)=O.[Na+].C1COCC1.Cl[C:30]([O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:31]>C(Cl)Cl>[C:8]([C:6]1[CH:5]=[C:4]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[C:3]([O:17][CH3:18])=[C:2]([NH:1][C:30](=[O:31])[O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:7]=1)([CH3:10])([CH3:11])[CH3:9]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 15891Phenyl chloroformateHCID 516892Sodium BicarbonateHCID 10214710N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamide

Product 1

HCID 86275692Phenyl 5-tert-butyl-2-methoxy-3-(methylsulfonamido)phenylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under N2 was charged the product of step (ix) above (167.0 g, 613 mmol), NaHCO3 (77.3 g, 920 mmol), THF (870 mL) and DCM (1440 mL). Phenyl chloroformate (82.6 mL, 659 mmol) was added dropwise, while maintaining the temperature below 20° C., and the reaction was stirred at room temperature for 4 h. HPLC analysis of the reaction mixture indicated 98.6% product and 0.03% starting material. The reaction mixture was filtered and the cake was washed with THF (˜50 mL). The filtrate was concentrated to ˜900 mL and cyclohexane (2400 mL) was added, then the mixture was left to stir overnight. The resulting solid was collected via vacuum filtration and washed with cyclohexane (500 mL). The pale pink solid produced was dried, under vacuum, at 40° C. for 4 h. Yield=232.6 g (96.7%). HPLC purity 94.5%. 1H NMR purity >95%.

Workup

  1. temperaturewhile maintaining the temperature below 20° C.
  2. filtrationThe reaction mixture was filtered
  3. washthe cake was washed with THF (˜50 mL)
  4. concentrationThe filtrate was concentrated to ˜900 mL and cyclohexane (2400 mL)
  5. additionwas added
  6. waitthe mixture was left
  7. stirringto stir overnight
  8. filtrationThe resulting solid was collected via vacuum filtration
  9. washwashed with cyclohexane (500 mL)
  10. customThe pale pink solid produced
  11. customwas dried, under vacuum, at 40° C. for 4 h

Sources & evidence

ORD record
ord-b06a2fa79d3845118f09ae869e24b34f
Source dataset
uspto-grants-2015_01
Patent number
US08927563B2

Reaction notes

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