Thiazole → Tert-butyl 4-hydroxy-4-(1,3-thiazol-2-yl)cyclohexanecarboxylate

HRID 410440Notes

Reaction equation

HRID 410440 reaction equation
C([Mg]Cl)(C)C.[Cl-].[Li+].[S:8]1[CH:12]=[CH:11][N:10]=[CH:9]1.[O:13]=[C:14]1[CH2:19][CH2:18][CH:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1>C1COCC1>[OH:13][C:14]1([C:9]2[S:8][CH:12]=[CH:11][N:10]=2)[CH2:15][CH2:16][CH:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]1

Participants

5

Reactant 3

HCID 9256ThiazoleHCID 14940589tert-Butyl 4-oxocyclohexane-1-carboxylateHCID 178461733HCID 178461733, compound

Product 1

HCID 67257275Tert-butyl 4-hydroxy-4-(1,3-thiazol-2-yl)cyclohexanecarboxylateYield 80.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a flask containing THF (82 mL) was added isopropylmagnesium chloride/lithium chloride (1.2 M in THF, 37.7 mL, 45 mmol). A solution of thiazole (3.5 g, 41 mmol) in THF (20 mL) was added slowly. The reaction was stirred for one hour. A solution of tert-butyl 4-oxocyclohexanecarboxylate (12.23 g, 62 mmol) in THF (20 mL) was added and the reaction was stirred for 3 hours. The reaction was then quenched slowly with saturated ammonium chloride and diluted with ethyl acetate. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated. Flash chromatography was used for purification to yield tert-butyl 4-hydroxy-4-(1,3-thiazol-2-yl)cyclohexanecarboxylate (9.25 g, 33 mmol, 79% yield). MS ESI: [M+H]+ m/z 284.1.

Workup

  1. stirringthe reaction was stirred for 3 hours
  2. customThe reaction was then quenched slowly with saturated ammonium chloride
  3. additiondiluted with ethyl acetate
  4. customThe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customFlash chromatography was used for purification

Sources & evidence

ORD record
ord-3efb611faba1468a8551c0fdb7d85fc4
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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