Thiazole → HCID 178458940, compound

HRID 2272665Notes

Reaction equation

HRID 2272665 reaction equation
[Cl-].[Li+].C([Mg]Cl)(C)C.[S:8]1[CH:12]=[CH:11][N:10]=[CH:9]1.[C:13]([C@H:17]1[CH2:22][CH2:21][C@H:20]([C:23]([O:25][CH3:26])=[O:24])[CH2:19][CH2:18]1)(=[O:16])[CH2:14][CH3:15]>C1COCC1>[OH:16][C:13]([C@H:17]1[CH2:22][CH2:21][C@H:20]([C:23]([O:25][CH3:26])=[O:24])[CH2:19][CH2:18]1)([C:9]1[S:8][CH:12]=[CH:11][N:10]=1)[CH2:14][CH3:15]

Participants

5

Reactant 3

HCID 9256ThiazoleHCID 178459256HCID 178459256, compoundHCID 178461733HCID 178461733, compound

Product 1

HCID 178458940HCID 178458940, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Isopropyl magnesium chloride lithium chloride (1.3 M in THF, 6.66 mL, 8.66 mmol) was added drop-wise to a solution of thiazole (0.675 mL, 9.44 mmol) in THF (5 mL) at 0° C. The reaction was stirred for 30 minutes and the ice bath was removed. Stirring was then continued for 10 minutes before the reaction was re-cooled in an acetone/dry ice bath, then a solution of methyl trans-4-propanoylcyclohexanecarboxylate (1.56 g, 7.87 mmol) in THF (15 mL) was transferred in via cannula. The reaction was stirred for 1 hour and the cooling bath was removed. Once warming was complete (˜1 hour) the reaction was diluted with saturated aqueous ammonium chloride (75 mL) and the resulting biphasic mixture was transferred to a separatory funnel. The organic phase was diluted with ethyl acetate (125 mL). The organic phase was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes) to afford trans-methyl 4-[1-hydroxy-1-(1,3-thiazol-2-yl)propyl]cyclohexanecarboxylate. MS ESI calc'd. for C14H22NO3S [M+H]+ 284. found 284. 1H NMR (500 MHz, DMSO-d6) δ 7.70 (d, J=3.3 Hz, 1H), 7.49 (d, J=3.3 Hz, 1H), 3.53 (s, 3H), 2.07 (t, J=12.1 Hz, 1H), 1.95-1.63 (m, 4H), 1.44-1.06 (m, 6H), 1.01-0.81 (m, 2H), 0.65 (t, J=7.3 Hz, 3H).

Workup

  1. customthe ice bath was removed
  2. stirringStirring
  3. waitwas then continued for 10 minutes before the reaction
  4. temperaturewas re-cooled in an acetone/dry ice bath
  5. stirringThe reaction was stirred for 1 hour
  6. customthe cooling bath was removed
  7. temperatureOnce warming
  8. custom(˜1 hour)
  9. additionwas diluted with saturated aqueous ammonium chloride (75 mL)
  10. customthe resulting biphasic mixture was transferred to a separatory funnel
  11. additionThe organic phase was diluted with ethyl acetate (125 mL)
  12. customThe organic phase was separated
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-bc36d4701fcf4851aed826d0d817c90e
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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