Hydrochloric Acid → HCID 87546368, compound

HRID 1435694Notes

Reaction equation

HRID 1435694 reaction equation
[H-].[Na+].FC(F)(F)S(Cl)(=O)=O.FC(F)(F)S([O:16][CH2:17][C:18]([F:21])([F:20])[F:19])(=O)=O.[Cl:24][C:25]1[C:26]([CH3:43])=[C:27]([S:31]([NH:34][C:35]2[S:36][CH:37]=[C:38]([CH2:40][CH2:41]O)[N:39]=2)(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=1.Cl>C1COCC1>[Cl:24][C:25]1[C:26]([CH3:43])=[C:27]([S:31]([NH:34][C:35]2[S:36][CH:37]=[C:38]([CH2:40][CH2:41][O:16][CH2:17][C:18]([F:19])([F:20])[F:21])[N:39]=2)(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydride3×HCID 79000Trifluoromethanesulfonyl chlorideHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonate2×HCID 87545745HCID 87545745, compound

Product 1

HCID 87546368HCID 87546368, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Sodium hydride (95% dry, 253 mg, 10.00 mmol) was added to a stirred solution of 2,2,2-tirluoroethanol (1.00 g, 10.00 mmol) in THF (15 mL) at 0° C. under nitrogen atmosphere. After stirring for 15 minutes at room temperature, the temperature was lowered to −80° C. using an ethanol-dry ice bath. Trifluoromethanesulfonyl chloride (1.69 g, 10.00 mmol) dissolved in THF (5 mL) was then added in small portions, and the mixture was then left to reach room temperature over night. The reaction mixture was centrifuged and the white precipitate was separated. The solvent was diluted with THF to 25 mL (assumed concentration: 0.4 M). The prepared 2,2,2-trifluoroethyl trifluoromethanesulfonate solution (7.5 mL, 0.4 M) was added to a mixture of EXAMPLE 181A (500 mg, 1.5 mmol) and sodium hydride (95% dry, 94 mg, 3.73 mmol) in THF (10 mL) at 0° C. under nitrogen atmosphere. After stirring at 0° C. for 1.5 h an additional amount of sodium hydride (95% dry, 76 mg, 3.00 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate solution (7.5 mL) was added. After 1 h at 0° C. was die mixture poured on to ice and neutralized with 2.0 M HCl and extracted with DCM. Evaporation of the organic solvent gave a residue which was purified by flash chromatography on silica gel eluting with a 2-5% acetone gradient in DCM. This gave 174 mg (28%) of a white solid: MS (Ionspray, [M+H]+) m/z 414. Anal. Calcd. (found) for C14H14ClF3N2O3S2: C, 40.5 (40.5)%; H, 3.4 (3.4)%; N, 6.7 (6.7)%.

Workup

  1. customwas lowered to −80° C.
  2. additionwas then added in small portions
  3. waitthe mixture was then left
  4. waitto reach room temperature over night
  5. customthe white precipitate was separated
  6. additionThe solvent was diluted with THF to 25 mL (assumed concentration: 0.4 M)
  7. additionwas added
  8. waitAfter 1 h at 0° C. was
  9. extractionextracted with DCM
  10. customEvaporation of the organic solvent
  11. customgave a residue which
  12. customwas purified by flash chromatography on silica gel eluting with a 2-5% acetone gradient in DCM

Sources & evidence

ORD record
ord-2dd63ca5a5814b709f8dfdf480ace5f1
Source dataset
uspto-grants-2009_11
Patent number
US07618961B2

Reaction notes

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