Tetrabutylammonium Fluoride → 3-[(1S)-2-hydroxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]-N-1,3-thiazol-2-ylbenzamide

HRID 20486Notes

Reaction equation

HRID 20486 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH2:27][C@H:28]([CH3:55])[O:29][C:30]1[CH:31]=[C:32]([CH:41]=[C:42]([O:44][C:45]2[CH:50]=[CH:49][C:48]([S:51]([CH3:54])(=[O:53])=[O:52])=[CH:47][CH:46]=2)[CH:43]=1)[C:33]([NH:35][C:36]1[S:37][CH:38]=[CH:39][N:40]=1)=[O:34])(C(C)(C)C)(C)C>C1COCC1.C(OCC)C.Cl>[OH:26][CH2:27][C@H:28]([CH3:55])[O:29][C:30]1[CH:31]=[C:32]([CH:41]=[C:42]([O:44][C:45]2[CH:50]=[CH:49][C:48]([S:51]([CH3:54])(=[O:52])=[O:53])=[CH:47][CH:46]=2)[CH:43]=1)[C:33]([NH:35][C:36]1[S:37][CH:38]=[CH:39][N:40]=1)=[O:34]

Participants

6

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride2×HCID 593468793-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]-N-1,3-thiazol-2-ylbenzamide

Product 1

HCID 116623323-[(1S)-2-hydroxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]-N-1,3-thiazol-2-ylbenzamideYield 60%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Tetra-n-butyl ammonium fluoride (1.0M in THF, 0.832 mL, 0.832 mmol) was added to a solution of 3-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]-N-1,3-thiazol-2-ylbenzamide (425 mg, 0.756 mmol) in THF (5 mL) and the reaction stirred for 1.5 h. A further portion of tetra-n-butyl ammonium fluoride (0.83 mL) in THF was added and the reaction was stirred for a further 1.5 h. The reaction was then diluted with diethyl ether (40 mL) and 1M aqueous hydrochloric acid (20 mL) and the aqueous layer was re-extracted with diethyl ether (20 mL). The combined organic layers were dried (MgSO4), filtered and evaporated. Purification by column chromatography, eluting with 50% to 100% ethyl acetate in hexanes, afforded the title compound as a foam (200 mg, 60%). 1H NMR δ (CDCl3): 1.30 (d, 3H), 3.08 (s, 3H), 3.77 (m, 2H), 4.47 (m, 1H), 6.85 (s, 1H), 7.00 (d, 1H), 7.13 (d, 2H), 7.20 (s, 1H), 7.32 (d, 1H), 7.37 (s, 1H), 7.92 (d, 2H). m/z 467 (M−H)−

Workup

  1. stirringthe reaction was stirred for a further 1.5 h
  2. extractionthe aqueous layer was re-extracted with diethyl ether (20 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customPurification by column chromatography
  7. washeluting with 50% to 100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-94f5eff9894d45f28525285f6416eb49
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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