Sodium Bicarbonate → Methyl 3-(2-oxa-6-azaspiro[3.3]heptan-6-ylsulfonyl)-5-(trifluoromethyl)benzoate

HRID 878354Notes

Reaction equation

HRID 878354 reaction equation
Cl[S:2]([C:5]1[CH:6]=[C:7]([CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1)[C:8]([O:10][CH3:11])=[O:9])(=[O:4])=[O:3].C(O)(=O)C(O)=O.[CH2:25]1[C:28]2([CH2:31][NH:30][CH2:29]2)[CH2:27][O:26]1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:25]1[C:28]2([CH2:31][N:30]([S:2]([C:5]3[CH:6]=[C:7]([CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=3)[C:8]([O:10][CH3:11])=[O:9])(=[O:4])=[O:3])[CH2:29]2)[CH2:27][O:26]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 53308464Oxalic acid--2-oxa-6-azaspiro(3.3)heptane (1/1)HCID 62631505Methyl 3-(chlorosulfonyl)-5-(trifluoromethyl)benzoate

Product 1

HCID 70663194Methyl 3-(2-oxa-6-azaspiro[3.3]heptan-6-ylsulfonyl)-5-(trifluoromethyl)benzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cooled solution of methyl 3-(chlorosulfonyl)-5-(trifluoromethyl)benzoate (1 g, 1.33 mmol, Buttpark Ltd.) in CH2Cl2 (10 mL) was added N,N-ethyldiisopropylamine (1.28 g, 1.73 mL, 9.91 mmol, Eq: 3) and 2-oxa-6-aza-spiro[3.3]heptane oxalate (524 mg, 1.82 mmol). The reaction mixture was stirred for 2 hours at room temperature. The reaction mixture was poured on 30 mL 10% aqueous NaHCO3 solution and 30 mL CH2Cl2 and the layers were separated. The aqueous layer was extracted a second time with 30 mL CH2Cl2. The organic layers were washed with 30 mL brine, dried over MgSO4, filtered and concentrated under vacuum. The compound was purified by silica gel chromatography on a 20 g column using an MPLC (Flashmaster) system eluting with a gradient of n-heptane:EtOAc (100:0 to 30:70). Colorless solid (460 mg, 38.1%). MS (ESI): m/z=365 [M+H]+.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted a second time with 30 mL CH2Cl2
  3. washThe organic layers were washed with 30 mL brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe compound was purified by silica gel chromatography on a 20 g column
  8. washeluting with a gradient of n-heptane:EtOAc (100:0 to 30:70)

Sources & evidence

ORD record
ord-dc61798b902d412e9cd7b448abf52a5b
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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