Epibromohydrin → HCID 9947844, compound

HRID 1953820Notes

Reaction equation

HRID 1953820 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH2:15][C:16]#[N:17])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.C[Li].[CH2:20]([CH:22]1[O:24][CH2:23]1)Br.C[Mg]I>O1CCCC1.C(OCC)C.[Cl-].[NH4+].O>[C:16]([C:15]1([C:9]2[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:7]([O:6][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[CH:8]=2)[CH2:23][CH:22]([OH:24])[CH2:20]1)#[N:17]

Participants

9

Reactant 4

HCID 18430EpibromohydrinHCID 107282283-(Cyclopentyloxy)-4-methoxyphenylacetonitrileHCID 178418348HCID 178418348, compoundHCID 178418373HCID 178418373, compound

Product 1

HCID 9947844HCID 9947844, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A solution of (3-cyclopentyloxy-4-methoxyphenyl)acetonitrile (prepared as described in U.S. Pat. No. 5,631,284) (12.65 g, 54.7 mmol) in tetrahydrofuran (400 mL) and examethylphosphoramide (16 mL) at -78° C. under an argon atmosphere was first treated dropwise over 75 min with 1.4 M methyllithium in diethyl ether (47 mL, 65.6 mmol), then with epibromohydrin (5.6 mL, 65.6 mmol). The reaction was allowed to warm to room temperature and was stirred for 3 h, then was recooled to -78° C. and was treated dropwise over 0.5 h with 3.0 M methylmagnesium iodide in diethyl ether. The reaction was stirred at room temperature for 20 h, diluted with aqueous ammonium chloride and water, and was extracted three times with tertbutyl methyl ether. The organic extract was dried (magnesium sulfate), was evaporated and was partially purified by flash chromatography, eluting with 35:65 ethyl acetate:hexanes to provide a mixture of cis- and trans-3-cyano-3-(3-cyclopentyloxy-4-methoxyphenyl)cyclobutan-1-ol and cis- and trans-2-cyano-2-(3-cyclopentyloxy-4-methoxyphenyl)-1-cyclopropylmethanol (~9: 1, by 1H-NMR) as a dark orange oil (10.01 g, 64%).

Workup

  1. customwas recooled to -78° C.
  2. stirringThe reaction was stirred at room temperature for 20 h
  3. extractionwas extracted three times with tertbutyl methyl ether
  4. extractionThe organic extract
  5. dry with materialwas dried (magnesium sulfate)
  6. customwas evaporated
  7. customwas partially purified by flash chromatography
  8. washeluting with 35:65 ethyl acetate
  9. customhexanes to provide

Sources & evidence

ORD record
ord-d0d7200f37134f34a31f5d4545420951
Source dataset
uspto-grants-2000_09
Patent number
US06118017

Reaction notes

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