Acetic Acid → HCID 86653598, compound

HRID 1892004Notes

Reaction equation

HRID 1892004 reaction equation
[Si]([O:18][CH2:19][CH:20]1[CH2:25][C:24]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([C:34]([F:37])([F:36])[F:35])[CH:28]=2)([CH3:26])[C:23]([C:38]([O:40][CH3:41])=[O:39])=[CH:22][CH2:21]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C(OCC)(=O)C>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([C:24]2([CH3:26])[C:23]([C:38]([O:40][CH3:41])=[O:39])=[CH:22][CH2:21][CH:20]([CH2:19][OH:18])[CH2:25]2)=[CH:28][C:29]=1[C:34]([F:35])([F:36])[F:37]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 2724141Tetrabutylammonium FluorideHCID 86653596HCID 86653596, compound

Product 1

HCID 86653598HCID 86653598, compoundYield 94.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl (4RS,6RS)-4-((tert-butyl-diphenylsilyloxy)methyl)-6-(4-chloro-3-(trifluoromethyl)-phenyl)-6-methylcyclohex-1-enecarboxylate (495 mg, 0.823 mmol) in THF (5 mL) was treated at rt with acetic acid (0.118 mL, 2.058 mmol), followed by tetrabutylammonium fluoride (1.0 M in THF, 1.235 mL, 1.235 mmol). The resulting solution was stirred for 17.5 h. After this time, the solution was diluted with ethyl acetate, washed sequentially with saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride, dried over sodium sulfate and then concentrated under vacuum to yield a residue. The residue was purified by column chromatography on silica gel, eluting with 20-50% ethyl acetate-hexane, to provide methyl (4RS,6RS)-6-(4-chloro-3-(trifluoromethyl)phenyl)-4-(hydroxymethyl)-6-methylcyclohex-1-enecarboxylate as a colorless gum (281 mg, 94%). Mass spectrum m/z 363.0 (M+H+). 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J=2.2 Hz, 1 H), 7.39 (d, J=8.6 Hz, 1 H), 7.32 (dd, J=8.6, 2.2 Hz, 17 H), 7.28 (dd, J=5.4, 2.5 Hz, 1 H), 3.64 (s, 3 H), 3.42 (m, 2 H), 2.45 (m, 1 H), 2.00 (m, 1 H), 1.76 (m, 1 H), 1.65 (s, 3 H), 1.53 (m, 2 H), 1.42 (br. s, 1 H).

Workup

  1. washwashed sequentially with saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customto yield a residue
  5. customThe residue was purified by column chromatography on silica gel
  6. washeluting with 20-50% ethyl acetate-hexane

Sources & evidence

ORD record
ord-3d662e060cf14098ab14e401bf242f5b
Source dataset
uspto-grants-2013_08
Patent number
US08507559B2

Reaction notes

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