Thiazole → HCID 178467442, compound

HRID 928105Notes

Reaction equation

HRID 928105 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Li]CCCC.[C:11]([C@H:14]1[CH2:19][CH2:18][C@H:17]([NH:20][C:21](=[O:30])[O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:16][CH2:15]1)(=[O:13])[CH3:12]>C1COCC1.O>[OH:13][C:11]([C@H:14]1[CH2:19][CH2:18][C@H:17]([NH:20][C:21](=[O:30])[O:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:16][CH2:15]1)([C:2]1[S:1][CH:5]=[CH:4][N:3]=1)[CH3:12]

Participants

6

Reactant 3

HCID 9256ThiazoleHCID 178418339ButyllithiumHCID 178468180HCID 178468180, compound

Product 1

HCID 178467442HCID 178467442, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of thiazole (740 mg, 8.72 mmol) in THF (87 mL) at −78° C. was added n-BuLi (2.5 M in hexanes, 3.84 mL, 9.59 mmol) and the solution was stirred for 30 minutes at −78° C. A solution of benzyl (trans-4-acetylcyclohexyl)carbamate (1.20 g, 4.36 mmol) in THF (5 mL) was added and the reaction was stirred for one hour at −78° C. The reaction was diluted with water and warmed to room temperature. The mixture was extracted with ethyl acetate and the organic layer was separated, dried over magnesium sulfate, filtered and concentrated in vacuo. Column chromatography on silica gel (0-10% methanol gradient in dichloromethane) afforded benzyl {trans-4-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]cyclohexyl}carbamate MS ESI calc'd. for C19H25N2O3S [M+H]+ 361. found 361. 1H NMR (500 MHz, DMSO-d6) δ 7.67 (d, J=3.2, 1H), 7.51 (d, J=3.2, 1H), 7.40-7.20 (m, 4H), 7.12 (d, J=8.0, 1H), 5.70 (s, 1H), 4.95 (s, 2H), 3.19-2.98 (m, 1H), 1.88-1.66 (m, 3H), 1.65-1.49 (m, 1H), 1.47-1.33 (m, 4H), 1.28-1.14 (m, 1H), 1.14-0.89 (m, 3H).

Workup

  1. stirringthe reaction was stirred for one hour at −78° C
  2. temperaturewarmed to room temperature
  3. extractionThe mixture was extracted with ethyl acetate
  4. customthe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9453757db26f4312a74f5fbdecedd62b
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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