2-Bromo-1-methoxy-4-(trifluoromethyl)benzene → HCID 57132321, compound

HRID 1417548Notes

Reaction equation

HRID 1417548 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[O:12][CH3:13].C([Li])(C)(C)C.[CH2:19]([O:26][CH2:27][C@H:28]1[CH2:37][CH2:36][C@:30]2([O:34][CH2:33][C:32](=[O:35])[CH2:31]2)[C@@H:29]1[C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1>[CH2:19]([O:26][CH2:27][C@H:28]1[CH2:37][CH2:36][C@:30]2([O:34][CH2:33][C@@:32]([OH:35])([C:2]3[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=3[O:12][CH3:13])[CH2:31]2)[C@@H:29]1[C:38]1[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 27570332-Bromo-1-methoxy-4-(trifluoromethyl)benzeneHCID 67671832HCID 67671832, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 57132321HCID 57132321, compoundYield 51.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

2-Bromo-4-(trifluoromethyl)anisole (227 mg, 0.89 mmol), prepared according to the procedure of J. Alexander (Org. Prep. Proced. Int., 1986, 18, 213-215), was dissolved in 3.7 mL of THF and cooled in a -78° C. bath. A solution of t-butyllithium (1.0 mL, 1.7M in hexane, 1.7 mmol) was added over a period of 2 min. After 30 min., a solution of 200 mg (0.56 mmol) of (5R,6S,7S)-7-(benzyloxymethyl)-6-(4-fluorophenyl)-1-oxaspiro[4.4]nonane-3-one (prepared from methyl (5R,6S,7S)-6-(4-fluorophenyl)-3-(methylene)-1-oxaspiro[4.4]nonane-7-carboxylate (from Example 9) by DIBALH reduction, benzylation with sodium hydride and benzyl bromide, and oxidation as described in Example 6, Step C) in 1.0 mL of THF was added, and the reaction was stirred for 45 min. at -78° C. followed by warming to -35° C. over 20 min. The reaction was quenched by the addition of 10 mL of saturated aqueous ammonium chloride and partioned between 30 mL of ethyl acetate and 10 mL of water. The organic layer was washed with 10 mL of saturated aqueous sodium bicarbonate and 10 mL of saturated aqueous sodium chloride, dried over sodium sulfate, decanted, and evaporated. The crude product was purified by flash column chromatography, eluting with 1.5-5% ethyl ether in toluene to give 154 mg of the title compound.

Workup

  1. temperatureby warming to -35° C. over 20 min
  2. customThe reaction was quenched by the addition of 10 mL of saturated aqueous ammonium chloride
  3. washThe organic layer was washed with 10 mL of saturated aqueous sodium bicarbonate and 10 mL of saturated aqueous sodium chloride
  4. dry with materialdried over sodium sulfate
  5. customdecanted
  6. customevaporated
  7. customThe crude product was purified by flash column chromatography
  8. washeluting with 1.5-5% ethyl ether in toluene

Sources & evidence

ORD record
ord-97c2f75ca48b41cea8624972fc8fbecf
Source dataset
uspto-grants-1999_03
Patent number
US05877191

Reaction notes

Loading…