N-(4-amino-2-fluorophenyl)methanesulfonamide → 8-Tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid-(3-fluoro-4-methanesulphonylaminophenyl)amide

HRID 1013333Notes

Reaction equation

HRID 1013333 reaction equation
[C:1]([CH:5]1[CH2:17][CH2:16][C:8]2([O:12][N:11]=[C:10]([C:13]([OH:15])=O)[CH2:9]2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])=[C:21]([F:30])[CH:20]=1>C1COCC1>[F:30][C:21]1[CH:20]=[C:19]([NH:18][C:13]([C:10]2[CH2:9][C:8]3([CH2:7][CH2:6][CH:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:17][CH2:16]3)[O:12][N:11]=2)=[O:15])[CH:24]=[CH:23][C:22]=1[NH:25][S:26]([CH3:29])(=[O:28])=[O:27]

Participants

4

Reactant 2

HCID 12254684N-(4-amino-2-fluorophenyl)methanesulfonamideHCID 579514498-Tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid

Product 1

HCID 673166198-Tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid-(3-fluoro-4-methanesulphonylaminophenyl)amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The acid 8-tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid (359 mg, 1.5 mmol) was dissolved in THF (15 ml). N,N′-carbonyldiimidazole (243.5 mg, 1.5 mmol) was added while stirring. For activation, the mixture was stirred for 1 h at RT. The N-(4-amino-2-fluorophenyl)methanesulphonamide (326.8 mg, 1.60 mmol) was then added as a solid. The course of the reaction was controlled by DC. After 3 d only small amounts of starting products could still be seen in the DC. For working up, THF was removed by distillation. The residue was dissolved in 0.5 N aq. HCl (10 ml) and EtOAc (40 ml). The phases were separated. The organic phase was washed successively with 0.5 N aq. HCl (2×8 ml), with water (1×10 ml), with 1.1 M aq. NaHCO3 solution (3×7 ml) and water (3×10 ml). The organic phase was dried with Na2SO4. The solvent was removed by distillation. The light brown residue was stirred out with diethyl ether (3×2 ml). The solvent was in each case removed by suction-filtration. The light pink residue was the mixture of the diastereoisomers of 8-tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid-(3-fluoro-4-methanesulphonylaminophenyl)amide (353 mg, mp 104-107° C. and 228-232° C., 55%).

Workup

  1. stirringFor activation, the mixture was stirred for 1 h at RT
  2. customTHF was removed by distillation
  3. dissolutionThe residue was dissolved in 0.5 N aq. HCl (10 ml)
  4. customThe phases were separated
  5. washThe organic phase was washed successively with 0.5 N aq. HCl (2×8 ml), with water (1×10 ml), with 1.1 M aq. NaHCO3 solution (3×7 ml) and water (3×10 ml)
  6. dry with materialThe organic phase was dried with Na2SO4
  7. customThe solvent was removed by distillation
  8. stirringThe light brown residue was stirred out with diethyl ether (3×2 ml)
  9. customremoved by suction-filtration
  10. additionthe mixture of the diastereoisomers of 8-tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid-(3-fluoro-4-methanesulphonylaminophenyl)amide (353 mg, mp 104-107° C. and 228-232° C., 55%)

Sources & evidence

ORD record
ord-87b0fadf713049f1ad534dd07fd04f2c
Source dataset
uspto-grants-2011_07
Patent number
US07981883B2

Reaction notes

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