Water → HCID 44612585, compound

HRID 1892006Notes

Reaction equation

HRID 1892006 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:23])[CH2:13][CH:12]([C:14]([O:16][CH3:17])=[O:15])[CH2:11][C:10](C(OC)=O)=[C:9]2[OH:22])=[CH:4][C:3]=1[C:24]([F:27])([F:26])[F:25].[Cl-].[Na+].O>CS(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:23])[C:9](=[O:22])[CH2:10][CH2:11][CH:12]([C:14]([O:16][CH3:17])=[O:15])[CH2:13]2)=[CH:4][C:3]=1[C:24]([F:25])([F:26])[F:27]

Participants

5

Reactant 3

HCID 962WaterHCID 5234Sodium ChlorideHCID 67158961HCID 67158961, compound

Product 1

HCID 44612585HCID 44612585, compoundYield 45.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
155 °C

Procedure

A solution of dimethyl 5-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxy-5-methylcyclohex-3-ene-1,3-dicarboxylate (mixture of diastereomers, 485 mg, 1.192 mmol) in DMSO (5 mL) was treated with sodium chloride (139 mg, 2.385 mmol) and water (0.107 mL, 5.96 mmol). The resulting mixture was bubbled with nitrogen for 15 min, and then heated under nitrogen on an oil bath at 150-160° C. for 4.5 h. After this time, the mixture was cooled to rt, diluted with water and then extracted three times with ethyl acetate. The combined organic layers were washed with water followed by saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under vacuum to yield a residue. The residue was purified by column chromatography on silica gel, eluting with 20-35% ethyl acetate-hexanes, to provide methyl (1RS,3RS)-3-(4-chloro-3-(trifluoromethyl)-phenyl)-3-methyl-4-oxocyclohexanecarboxylate (137 mg, 33%) and methyl (1SR,3RS)-3-(4-chloro-3-(trifluoro-methyl)phenyl)-3-methyl-4-oxocyclohexanecarboxylate (188 mg, 45%). The (1SR, 3RS) diastereomer could be partially converted to the (1RS, 3RS) diastereomer as described in the procedure of Example 7, Part 3.

Workup

  1. customThe resulting mixture was bubbled with nitrogen for 15 min
  2. temperatureAfter this time, the mixture was cooled to rt
  3. additiondiluted with water
  4. extractionextracted three times with ethyl acetate
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customto yield a residue
  9. customThe residue was purified by column chromatography on silica gel
  10. washeluting with 20-35% ethyl acetate-hexanes

Sources & evidence

ORD record
ord-9885c4caca6349b691d44dd58551ee31
Source dataset
uspto-grants-2013_08
Patent number
US08507559B2

Reaction notes

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