Triethylamine → methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-(4-chlorobutyryl-amino)-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate

HRID 927989Notes

Reaction equation

HRID 927989 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][C:5](Cl)=[O:6].[CH3:8][O:9][C:10]([N:12]([C:24]1[C:33]([C:34]([O:36][CH3:37])=[O:35])=[C:32]2[C:27]([CH:28]3[CH2:38][CH:29]3[CH2:30][O:31]2)=[CH:26][CH:25]=1)[S:13]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[NH2:23])(=[O:15])=[O:14])=[O:11].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C1COCC1>[CH3:8][O:9][C:10]([N:12]([C:24]1[C:33]([C:34]([O:36][CH3:37])=[O:35])=[C:32]2[C:27]([CH:28]3[CH2:38][CH:29]3[CH2:30][O:31]2)=[CH:26][CH:25]=1)[S:13]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[NH:23][C:5](=[O:6])[CH2:4][CH2:3][CH2:2][Cl:1])(=[O:14])=[O:15])=[O:11]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 783704-Chlorobutyryl chlorideHCID 516892Sodium BicarbonateHCID 86713323methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(2-amino-4-fluorobenzenesulfonyl)amino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 86713322methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-(4-chlorobutyryl-amino)-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylateYield 90.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Chlorobutyryl chloride (3.0 g) was added to a stirred, cooled solution of methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(2-amino-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 110, 0.135 g) and triethylamine (1.0 g) in THF (10 mL) at 0° C. On completion of the addition, the mixture was stirred at room temperature for 4 hours. Saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and petroleum ether, with a gradient of 20-25% to give methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-(4-chlorobutyrylamino)-4-fluoro-benzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (0.15 g) as a yellow oil.

Workup

  1. additionOn completion of the addition
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customThe filtrate was evaporated to dryness
  6. customthe residue was purified by chromatography on silica
  7. washeluting with a mixture of ethyl acetate and petroleum ether, with a gradient of 20-25%

Sources & evidence

ORD record
ord-a0b25da223354251ba1fe580f2772d14
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

Loading…