Methanesulfonyl chloride → HCID 118108918, compound

HRID 716149Notes

Reaction equation

HRID 716149 reaction equation
[C:1]([O:9][C@H:10]1[C:14]([F:16])([F:15])[CH:13](O)[O:12][C@@H:11]1[CH2:18][O:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:29][O:30][NH2:31].C1(C)C=C[C:35]([S:38]([O-])(=[O:40])=[O:39])=CC=1.[NH+]1C=CC=CC=1.C(=O)([O-])O.[Na+].CS(Cl)(=O)=O>C(#N)C.O.O1CCCC1.C(N(CC)CC)C>[C:20]([O:19][CH2:18][C@@H:11]([O:12][S:38]([CH3:35])(=[O:40])=[O:39])[C@@H:10]([O:9][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:14]([F:15])([F:16])/[CH:13]=[N:31]/[O:30][CH3:29])(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

9

Reactant 5

HCID 31297Methanesulfonyl chlorideHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 516892Sodium Bicarbonate2×HCID 521874O-Methylhydroxylamine hydrochlorideHCID 11760620143157-22-6

Product 1

HCID 118108918HCID 118108918, compoundYield 127.5%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

190 mg of (2R,3R)-2-((benzoyloxy)methyl)-4,4-difluoro-5-hydroxyoxolan-3-yl benzoate was dissolved in 4 mL of a mixed solvent of acetonitrile/water (3/1), and thereafter, 83.5 mg of O-methylhydroxylamine hydrochloride and 0.09 mL of triethylamine were added to the obtained solution. The thus obtained mixture was then stirred for 2 hours. Thereafter, 82 mg of pyridinium p-toluenesulfonate was added to the reaction mixture, and the thus obtained mixture was then stirred for 69 hours. Thereafter, a saturated sodium hydrogen carbonate aqueous solution was added to the reaction mixture, and the water layer was then removed. The water layer was extracted with ethyl acetate, and the organic layer was then combined with the extract. The thus obtained mixture was washed with a saturated sodium chloride aqueous solution, and was then dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure to obtain a colorless oily product. 0.42 mL of triethylamine was added to a solution of this oily product in 3 mL of tetrahydrofuran, and 0.12 mL of methanesulfonyl chloride was then added to the mixture at 0° C. The obtained mixture was stirred for 30 minutes. Thereafter, a saturated sodium hydrogen carbonate aqueous solution was added to the reaction mixture, and the water layer was then removed. The water layer was extracted with ethyl acetate, and the organic layer was then combined with the extract. The thus obtained mixture was washed with a saturated sodium chloride aqueous solution, and was then dried over anhydrous sodium sulfate. After that, the solvent was distilled away under reduced pressure, so as to obtain 202 mg of (2R,3R,5E)-3-benzoyloxy-4,4-difluoro-2-(methylsulfonyloxy)-5-(methoxyimino)pentyl benzoate in the form of a colorless oily product.

Workup

  1. stirringthe thus obtained mixture was then stirred for 69 hours
  2. customthe water layer was then removed
  3. extractionThe water layer was extracted with ethyl acetate
  4. washThe thus obtained mixture was washed with a saturated sodium chloride aqueous solution
  5. dry with materialwas then dried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled away under reduced pressure
  7. customto obtain a colorless oily product
  8. stirringThe obtained mixture was stirred for 30 minutes
  9. customthe water layer was then removed
  10. extractionThe water layer was extracted with ethyl acetate
  11. washThe thus obtained mixture was washed with a saturated sodium chloride aqueous solution
  12. dry with materialwas then dried over anhydrous sodium sulfate
  13. distillationAfter that, the solvent was distilled away under reduced pressure

Sources & evidence

ORD record
ord-3612e2536f2044899ddb8629a0541cd6
Source dataset
uspto-grants-2015_11
Patent number
US09187514B2

Reaction notes

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