HCID 178418365, compound → HCID 178472371, compound

HRID 928113Notes

Reaction equation

HRID 928113 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7]([C@H:9]2[CH2:14][CH2:13][C@H:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][CH2:10]2)=[O:8])=[N:4][CH:3]=1.[CH:20]([Mg]Br)([CH3:22])[CH3:21]>C1COCC1>[Br:1][C:2]1[S:6][C:5]([C:7]([C@H:9]2[CH2:10][CH2:11][C@H:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:13][CH2:14]2)([OH:8])[CH:20]([CH3:22])[CH3:21])=[N:4][CH:3]=1

Participants

4

Reactant 2

HCID 178418365HCID 178418365, compoundHCID 178472369HCID 178472369, compound

Product 1

HCID 178472371HCID 178472371, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of ethyl trans-4-[(5-bromo-1,3-thiazol-2-yl)carbonyl]cyclohexanecarboxylate (800 mg, 2.31 mmol) in anhydrous THF (16 ml) was treated dropwise over 1 h with isopropylmagnesium bromide (2.31 mmol, 2 M, 1.15 mL) at 0° C. under a nitrogen atmosphere. After stirring at 0° C. for 15 min, the reaction was allowed to reach room temperature. After 1 h, the reaction mixture was quenched with saturated ammonium chloride and taken up in ethyl acetate, washed with brine and dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (0% to 20% EtOAc in hexanes) and then by preparative HPLC reverse phase (C-18) eluting with 55% to 100% water in acetonitrile (0.1% trifluoroacetic acid). The collected fractions were diluted with ethyl acetate and washed with saturated sodium bicarbonate, brine, dried over magnesium sulfate, filtered and concentrated in vacuo to afford racemic ethyl trans-4-[1-(5-bromo-1,3-thiazol-2-yl)-1-hydroxy-2-methylpropyl]cyclohexanecarboxylate as a white solid. MS ESI calc'd. for C16H24BrNO3S [M+H]+ 390, 392. found 390, 392. 1H NMR (500 MHz, CDCl3) δ 7.60 (s, 1H), 4.10 (q, J=7.1, 2H), 2.30-2.20 (m, 1H), 2.17-2.06 (m, 1H), 2.05-1.79 (m, 2H), 1.93-1.81 (m, 1H), 1.62-1.50 (m, 1H), 1.48-1.20 (m, 5H), 1.22 (t, J=7.1, 3H), 0.88 (d, J=9.8, 3H), 0.87 (d, J=9.8, 3H).

Workup

  1. customto reach room temperature
  2. waitAfter 1 h
  3. customthe reaction mixture was quenched with saturated ammonium chloride
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography on silica gel (0% to 20% EtOAc in hexanes)
  9. washby preparative HPLC reverse phase (C-18) eluting with 55% to 100% water in acetonitrile (0.1% trifluoroacetic acid)
  10. additionThe collected fractions were diluted with ethyl acetate
  11. washwashed with saturated sodium bicarbonate, brine
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ff886c0ca1834de5abb04754d2a79b23
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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