Hydrochloric Acid → (S)-1-((R)-5-(2,5-difluorophenyl)-2-((methoxy-methoxy)methyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-2-hydroxypropan-1-one

HRID 270521Notes

Reaction equation

HRID 270521 reaction equation
[Si]([O:18][C@@H:19]([CH3:46])[C:20]([N:22]1[N:26]=[C:25]([C:27]2[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=2[F:34])[S:24][C@@:23]1([CH2:41][O:42][CH2:43][O:44][CH3:45])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:21])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].Cl>C1COCC1>[F:34][C:28]1[CH:29]=[CH:30][C:31]([F:33])=[CH:32][C:27]=1[C:25]1[S:24][C@@:23]([CH2:41][O:42][CH2:43][O:44][CH3:45])([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[N:22]([C:20](=[O:21])[C@@H:19]([OH:18])[CH3:46])[N:26]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2724141Tetrabutylammonium FluorideHCID 67214650(S)-2-(tert-butyldiphenylsilyloxy)-1-((R)-5-(2,5-difluorophenyl)-2-((methoxymethoxy)methyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)propan-1-one

Product 1

HCID 67214881(S)-1-((R)-5-(2,5-difluorophenyl)-2-((methoxy-methoxy)methyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-2-hydroxypropan-1-oneYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (0° C.) solution of (S)-2-(tert-butyldiphenylsilyloxy)-1-((R)-5-(2,5-difluorophenyl)-2-((methoxymethoxy)methyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)propan-1-one (110 mg, 0.17 mmol) in THF (10 mL) was added TBAF (0.28 mL, 1.0 M, 0.28 mmol). After slowly warming to room temperature and stirring for 16 hours, the mixture was treated with 0.5 N HCl (30 mL) and extracted with ethyl acetate (2×30 mL). The combined organics were washed with NaHCO3 (30 mL) and brine (30 mL), dried over Na2SO4, and concentrated under reduced pressure. The pale yellow residue was chromatographed (9:1 to 4:1 hexanes/ethyl acetate) to provide the product as a white solid (0.045 g, 64%).

Workup

  1. extractionextracted with ethyl acetate (2×30 mL)
  2. washThe combined organics were washed with NaHCO3 (30 mL) and brine (30 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe pale yellow residue was chromatographed (9:1 to 4:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-8706e96d6ce546b38511116654999c6c
Source dataset
uspto-grants-2008_11
Patent number
US07449486B2

Reaction notes

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