Tetrabutylammonium Fluoride → (9-(2-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 1255308Notes

Reaction equation

HRID 1255308 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Si]([O:26][CH2:27][CH2:28][C:29]1[C:30]([F:57])=[C:31]([CH:54]=[CH:55][CH:56]=1)[CH2:32][N:33]1[CH2:53][CH2:52][C:36]2([O:41][CH2:40][CH2:39][N:38]([C:42]([C:44]3[N:45]=[C:46]([CH:49]([CH3:51])[CH3:50])[S:47][CH:48]=3)=[O:43])[CH2:37]2)[CH2:35][CH2:34]1)(C(C)(C)C)(C)C>C1COCC1>[F:57][C:30]1[C:29]([CH2:28][CH2:27][OH:26])=[CH:56][CH:55]=[CH:54][C:31]=1[CH2:32][N:33]1[CH2:34][CH2:35][C:36]2([O:41][CH2:40][CH2:39][N:38]([C:42]([C:44]3[N:45]=[C:46]([CH:49]([CH3:51])[CH3:50])[S:47][CH:48]=3)=[O:43])[CH2:37]2)[CH2:52][CH2:53]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 58168600(9-(3-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-fluorobenzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Product 1

HCID 57989273(9-(2-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

TBAF (1M in THF, 13.9 mL) was added to a solution of (9-(3-(2-(tert-butyldimethylsilyloxy)ethyl)-2-fluorobenzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone [Example 7, step a] (5.35 g) in THF (50 mL) and the resulting mixture was stirred for 1 h. The solvent was evaporated and the residue partitioned between ethyl acetate (100 mL) and water (100 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with brine (100 mL), dried over sodium sulphate, filtered and evaporated. The crude material was purified by flash silica chromatography, elution gradient 4:1 isohexane:ethyl acetate to 100% ethyl acetate to give the subtitled compound as a clear oil. Yield 3.90 g.

Workup

  1. customThe solvent was evaporated
  2. customthe residue partitioned between ethyl acetate (100 mL) and water (100 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with ethyl acetate (2×100 mL)
  5. washThe combined organic phases were washed with brine (100 mL)
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude material was purified by flash silica chromatography, elution gradient 4:1 isohexane

Sources & evidence

ORD record
ord-4e127e89316c497ea1d4ebd22488279d
Source dataset
uspto-grants-2013_06
Patent number
US08455483B2

Reaction notes

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