HCID 178418630, compound → HCID 178501141, compound

HRID 2272653Notes

Reaction equation

HRID 2272653 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]([C@H:8]1[CH2:13][CH2:12][C@H:11]([C:14]([O:16][CH3:17])=[O:15])[CH2:10][CH2:9]1)=[O:7].[CH:18]1([Mg]Br)[CH2:20][CH2:19]1>C1COCC1>[CH:18]1([C:6]([OH:7])([C:2]2[S:1][CH:5]=[CH:4][N:3]=2)[C@H:8]2[CH2:9][CH2:10][C@H:11]([C:14]([O:16][CH3:17])=[O:15])[CH2:12][CH2:13]2)[CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 178418630HCID 178418630, compoundHCID 178501142HCID 178501142, compound

Product 1

HCID 178501141HCID 178501141, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl trans-4-(1,3-thiazol-2-ylcarbonyl)cyclohexanecarboxylate (2.59 g, 10.22 mmol) in THF (10 mL) at −78° C. was added cyclopropylmagnesium bromide (0.5 M in THF, 24 mL, 12.00 mmol) and the solution was stirred at this temperature for three hours. The solution was then allowed to warm for 15 minutes and then quenched with aqueous ammonium chloride. The solution was diluted with dichloromethane and the organic layer was separated, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (0-30% ethyl acetate/hexanes. The product was further purified by reverse phase chromatography (25-100% acetonitrile/water with 0.1% TFA modifier) to afford methyl trans-4-[cyclopropyl(hydroxy)1,3-thiazol-2-ylmethyl]cyclohexanecarboxylate. MS ESI calc'd. for C15H22NO3S [M+H]+ 296. found 296. 1H NMR (500 MHz, CDCl3) δ 7.77 (d, J=3.4 Hz, 1H), 7.37 (d, J=3.4 Hz, 1H), 3.65 (s, 3H), 2.28-2.17 (m, 1H), 2.13-2.02 (m, 3H), 2.01-1.90 (m, 2H), 1.56-1.48 (m, 1H), 1.48-1.39 (m, 1H), 1.39-1.32 (m, 1H), 1.33-1.19 (m, 3H), 0.75-0.62 (m, 1H), 0.61-0.50 (m, 1H), 0.42-0.25 (m, 2H).

Workup

  1. temperatureto warm for 15 minutes
  2. customquenched with aqueous ammonium chloride
  3. additionThe solution was diluted with dichloromethane
  4. customthe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel chromatography (0-30% ethyl acetate/hexanes
  9. customThe product was further purified by reverse phase chromatography (25-100% acetonitrile/water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-7837746898f242d1b9ace0f4b0a265fd
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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