Sodium hydride → HCID 21048980, compound

HRID 2212377Notes

Reaction equation

HRID 2212377 reaction equation
[CH2:1]([O:3][C:4](=[O:36])[CH:5]([S:32]([CH3:35])(=[O:34])=[O:33])[CH2:6][CH2:7][CH:8]1[CH2:13][CH2:12][C:11]([S:22]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)(=[O:24])=[O:23])([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[F:21])[CH2:10][CH2:9]1)[CH3:2].[H-].[Na+].FC(F)(F)S(O[CH2:45][CH3:46])(=O)=O>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:36])[C:5]([CH2:45][CH3:46])([S:32]([CH3:35])(=[O:33])=[O:34])[CH2:6][CH2:7][CH:8]1[CH2:9][CH2:10][C:11]([S:22]([C:25]2[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=2)(=[O:24])=[O:23])([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[F:21])[CH2:12][CH2:13]1)[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67924Ethyl trifluoromethanesulphonateHCID 21048985HCID 21048985, compound

Product 1

HCID 21048980HCID 21048980, compoundYield 12.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of the product from Example 108 (620 mg, 1.10 mmol) in N,N-dimethylformamide (2.5 mL) was added dropwise to a solution of sodium hydride (60% dispersion in mineral oil, 48 mg, 1.21 mmol) in N,N-dimethylformamide (2.5 mL), and stirred for 45 minutes. Ethyl trifluoromethanesulfonate (0.140 mL, 1.10 mmol) was added dropwise and stirred for 14 hours at room temperature. The reaction was partitioned between diethyl ether (150 mL) and 1M aqueous hydrochloric acid (150 mL), the phases were separated and the aqueous layer extracted with diethyl ether. The combined organic layers were washed with 1N aqueous sodium hydrogencarbonate and brine, dried over MgSO4 and concentrated. The residue was chromatographed using a Biotage™ 40S column, eluting with 70/30 iso-hexane/acetone to give the title compound (80 mg).

Workup

  1. stirringstirred for 14 hours at room temperature
  2. customThe reaction was partitioned between diethyl ether (150 mL) and 1M aqueous hydrochloric acid (150 mL)
  3. customthe phases were separated
  4. extractionthe aqueous layer extracted with diethyl ether
  5. washThe combined organic layers were washed with 1N aqueous sodium hydrogencarbonate and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was chromatographed
  9. washeluting with 70/30 iso-hexane/acetone

Sources & evidence

ORD record
ord-ef1a72314a2e4967a602500e8d6b2c98
Source dataset
uspto-grants-2006_09
Patent number
US07101895B2

Reaction notes

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