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

HRID 1039931Notes

Reaction equation

HRID 1039931 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 8028TetrahydrofuranSolvent2×

Procedure

To a flask containing TI-IF (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. additionTo a flask containing TI-IF (82 mL)
  2. stirringthe reaction was stirred for 3 hours
  3. customThe reaction was then quenched slowly with saturated ammonium chloride
  4. additiondiluted with ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customFlash chromatography was used for purification

Sources & evidence

ORD record
ord-678db9765ee340d4b0dc414f859646d3
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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