Water → 8-Hydroxy-8-(5-thiazolyl)-1,4-dioxaspiro[4.5]decane

HRID 1025748Notes

Reaction equation

HRID 1025748 reaction equation
[Si]([C:5]1[S:6][CH:7]=[CH:8][N:9]=1)(C)(C)C.C([Li])CCC.[CH2:15]1[O:25][C:18]2([CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]2)[O:17][CH2:16]1.O>C1COCC1.CCOC(C)=O>[S:6]1[C:7]([C:21]2([OH:24])[CH2:22][CH2:23][C:18]3([O:25][CH2:15][CH2:16][O:17]3)[CH2:19][CH2:20]2)=[CH:8][N:9]=[CH:5]1

Participants

7

Reactant 4

HCID 962WaterHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 5884532-TrimethylsilylthiazoleHCID 178418339Butyllithium

Product 1

HCID 590174418-Hydroxy-8-(5-thiazolyl)-1,4-dioxaspiro[4.5]decaneYield 90%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-TMS-thiazole (2.5 g, 15.89 mmol) was added to a solution of n-butyllithium (11.9 mL of 1.6 M solution in hexane, 19.07 mmol) in THF (20 mL) at −78° C. with stirring under N2. After being stirred at −78° C. for 0.5 h, a solution of 1,4-cyclohexanedione mono-ethylene ketal (2.48 g, 15.89 mmol) in THF (20 mL) was added to the lithiated compound solution via syringe and stirred for 1 h at −78° C. Water (5 mL) and EtOAc were added, and the reaction mixture was warmed to room temperature and extracted using EtOAc (3×). The combined organic layers were dried (MgSO4), filtered, and crystallized from EtOAc to yield 3.4 g of 8-(1,3-thiazol-5-yl)-1,4-dioxaspiro[4,5]decan-8-ol in 90% yield. MS (EI) calcd: (M+H)+=242.1; found: 242.1.

Workup

  1. stirringAfter being stirred at −78° C. for 0.5 h
  2. stirringstirred for 1 h at −78° C
  3. extractionextracted
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. customcrystallized from EtOAc

Sources & evidence

ORD record
ord-f949f88004d94aadaeab47bc0a211086
Source dataset
uspto-grants-2014_05
Patent number
US08729063B2

Reaction notes

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