Thiazole → HCID 178451153, compound

HRID 2272645Notes

Reaction equation

HRID 2272645 reaction equation
C([Mg]Cl)(C)C.[Li+].[Cl-].[S:8]1[CH:12]=[CH:11][N:10]=[CH:9]1.[C:13]([C@H:16]1[CH2:21][CH2:20][C@H:19]([C:22]([O:24][CH2:25][CH2:26][CH2:27][CH3:28])=[O:23])[CH2:18][CH2:17]1)(=[O:15])[CH3:14]>C1COCC1>[OH:15][C:13]([C@H:16]1[CH2:21][CH2:20][C@H:19]([C:22]([O:24][CH2:25][CH2:26][CH2:27][CH3:28])=[O:23])[CH2:18][CH2:17]1)([C:9]1[S:8][CH:12]=[CH:11][N:10]=1)[CH3:14]

Participants

5

Reactant 3

HCID 9256ThiazoleHCID 178451155HCID 178451155, compoundHCID 178461733HCID 178461733, compound

Product 1

HCID 178451153HCID 178451153, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) flask under nitrogen containing iPrMgCl—LiCl (1.3 M in THF, 55.2 mL, 71.8 mmol) was added thiazole (5.10 mL, 71.8 mmol) keeping the internal temperature <10° C. The resulting heterogenous mixture was warmed to RT where it was stirred for 10 min then re-cooled to −20° C. Then, a solution of butyl trans-4-acetylcyclohexanecarboxylate (12.5 g, 55.2 mmol) in THF (20+5 mL) was added via syringe. The cooling bath was then removed and the reaction mixture warmed slowly to 10° C. during which time it was observed to nearly completely homogenize. After 40 min, saturated aqueous NH4Cl followed by EtOAc were added and the layers separated, the organics dried over MgSO4, filtered and concentrated in vacuo. The crude residue was absorbed on silica and purified by flash chromatography to afford butyl trans-4-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]cyclohexanecarboxylate as a light yellow oil. The enantiomers were separated by chiral SFC (Chiral Technology AZ-H, 2.1×25 cm, 5 uM, 45/55 MeOH/CO2, Flow Rate: 80 mL/min, 6 min run time, WL: 220 nm) Elution was observed at 2.98 min and 4.14 min. Pooled fractions of each peak were separately concentrated under reduced pressure.

Workup

  1. customthe internal temperature <10° C
  2. temperatureThe resulting heterogenous mixture was warmed to RT where it
  3. temperaturethen re-cooled to −20° C
  4. customThe cooling bath was then removed
  5. temperaturethe reaction mixture warmed slowly to 10° C. during which time it
  6. stirringto nearly completely homogenize
  7. waitAfter 40 min
  8. additionwere added
  9. customthe layers separated
  10. dry with materialthe organics dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude residue was absorbed on silica
  14. custompurified by flash chromatography

Sources & evidence

ORD record
ord-a5fde4a6fbd64a0fbc9c51f62b0510a9
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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