HCID 178418630, compound → HCID 178472367, compound

HRID 928112Notes

Reaction equation

HRID 928112 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]1([Mg]Br)[CH2:22][CH2:21]1>C1COCC1.[Cl-].[NH4+].C(OCC)(=O)C>[Br:1][C:2]1[S:6][C:5]([C:7]([CH:20]2[CH2:22][CH2:21]2)([OH:8])[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)=[N:4][CH:3]=1

Participants

6

Reactant 2

HCID 178418630HCID 178418630, compound2×HCID 178472369HCID 178472369, compound

Product 1

HCID 178472367HCID 178472367, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A solution of ethyl trans-4-[(5-bromo-1,3-thiazol-2-yl)carbonyl]cyclohexanecarboxylate (518 mg, 1.49 mmol) in anhydrous THF (16 ml) was treated dropwise over 20 min with cyclopropylmagnesium bromide (1.49 mmol, 0.5 M in tetrahydrofuran, 2.99 mL) at 0° C. under a nitrogen atmosphere. After stirring 1 h at room temperature, additional cyclopropylmagnesium bromide (2.23 mmol, 0.5 M in tetrahydrofuran, 4.48 mL) was added dropwise over 20 min at 0° C. and then the mixture was allowed to reach room temperature. After 4 h the mixture was diluted with saturated ammonium chloride and ethyl acetate, washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (0% to 20% EtOAc in hexanes) to afford racemic ethyl trans-4-[(5-bromo-1,3-thiazol-2-yl)(cyclopropyl)hydroxymethyl]cyclohexanecarboxylate as a white solid. Two enantiomers were separated by chiral super critical fluid chromatography (Chiral Technology AS, 2.1×25 cm, 10 uM, 45/55 MeOH/CO2, Flow Rate: 70 mL/min, 14 min run time, WL: 220 nm) Elution was observed at 7.91 min and 10.78 min. Pooled fractions of each peak were concentrated under reduced pressure.

Workup

  1. customto reach room temperature
  2. washwashed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography on silica gel (0% to 20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-af197fe0c206452ab6b54e853ef33f8e
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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