Thiazole → Methyl 4-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]-1-methylcyclohexanecarboxylate

HRID 928131Notes

Reaction equation

HRID 928131 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Cl-].[Li+].C([Mg]Cl)(C)C.[C:13]([CH:16]1[CH2:21][CH2:20][C:19]([CH3:26])([C:22]([O:24][CH3:25])=[O:23])[CH2:18][CH2:17]1)(=[O:15])[CH3:14].[Cl-].[NH4+]>O1CCCC1>[OH:15][C:13]([CH:16]1[CH2:21][CH2:20][C:19]([CH3:26])([C:22]([O:24][CH3:25])=[O:23])[CH2:18][CH2:17]1)([C:2]1[S:1][CH:5]=[CH:4][N:3]=1)[CH3:14]

Participants

6

Reactant 4

HCID 9256ThiazoleHCID 25517Ammonium ChlorideHCID 19004752Methyl 4-acetyl-1-methylcyclohexanecarboxylateHCID 178461733HCID 178461733, compound

Product 1

HCID 70982839Methyl 4-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]-1-methylcyclohexanecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of thiazole (0.309 mL, 4.36 mmol) in tetrahydrofuran (5 mL) was added a solution of isopropylmagnesium chloride lithium chloride complex (1.0 M in tetrahydrofuran, 3.36 mL, 4.36 mmol). After 20 minutes, the resulting solution was added to a solution of methyl 4-acetyl-1-methylcyclohexanecarboxylate (864.9 mg, 4.36 mmol) in tetrahydrofuran (10 mL) via syringe over 6 minutes. After 90 minutes, saturated aqueous ammonium chloride solution (5 mL) was added to the reaction mixture and the resulting suspension was partitioned between water (5 mL) and ethyl acetate (30 mL). The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chiral chromatography (methanol/supercritical CO2) to give four separate stereoisomers (peak 1, peak 2, peak 3, peak 4) of methyl 4-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]-1-methylcyclohexanecarboxylate. MS ESI calc'd. for C14H21NO3S [M+H]+ 284. found 284.

Workup

  1. waitAfter 90 minutes
  2. customthe resulting suspension was partitioned between water (5 mL) and ethyl acetate (30 mL)
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chiral chromatography (methanol/supercritical CO2)
  8. customto give four
  9. customseparate stereoisomers (peak 1, peak 2, peak 3, peak 4) of methyl 4-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]-1-methylcyclohexanecarboxylate

Sources & evidence

ORD record
ord-3c099b529cf742778b7ee24985f74e7d
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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