Hydrochloric Acid → (4-Fluoro3-phenoxyphenyl)methyl 2-cyclopropyl-2-(4-chlorophenyl)ethyl ether

HRID 1383223Notes

Reaction equation

HRID 1383223 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([CH:22]2[CH2:24][CH2:23]2)[C:11](N2[C@@H](C(C)C)COC2=O)=[O:12])=[CH:6][CH:5]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32]Cl)=[CH:28][C:27]=1[O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.Cl>CN(C)C=O.O>[CH:22]1([CH:10]([C:7]2[CH:6]=[CH:5][C:4]([Cl:3])=[CH:9][CH:8]=2)[CH2:11][O:12][CH2:32][C:29]2[CH:30]=[CH:31][C:26]([F:25])=[C:27]([O:34][C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH:28]=2)[CH2:23][CH2:24]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 135636494-(Chloromethyl)-1-fluoro-2-phenoxybenzeneHCID 15616710(S)-N-[2-(4-chlorophenyl)-2-cyclopropylacetyl]-4-(1-methylethyl)-2-oxazolidinone

Product 1

HCID 15616708(4-Fluoro3-phenoxyphenyl)methyl 2-cyclopropyl-2-(4-chlorophenyl)ethyl ether

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

Under a nitrogen atmosphere a suspension of 0.06 gram (0.0024 mole) of 97% sodium hydride in 2.2 mL of dimethylformamide was stirred, and a solution of 0.40 gram (0.002 mole) of stereoisomer (A) of 2-cyclopropyl-2-(4-chlorophenyl)ethyl ethanol in 1.0 mL of dimethylformamide was slowly added. Upon completion of addition, the reaction mixture was stirred for 1.5 hours, and then a solution of 0.46 gram (0.0019 mole) of (4-fluoro-3-phenoxyphenyl)methyl chloride in 1.0 mL of dimethylformamide was added. Upon completion of addition, the reaction mixture was stirred for one hour, and then 2-3 mL of water was added. The mixture was poured into 75 mL of aqueous, 10% hydrochloric acid and then was extracted with two 50 mL portions of hexane. The combined hexane layers were washed with 25 mL of a saturated, aqueous solution of sodium chloride. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was subjected to rotating disk thin layer chromatography on silica gel using diethyl ether: hexane (19:1) as eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.55 gram of stereoisomer (A) of (4-fluoro-3-phenoxyphenyl)methyl 2-cyclopropyl-2-(4-chlorophenyl)ethyl ether as an oil. The nmr spectrum was consistent with the proposed structure. [α]D25 =(+)22.19°.

Workup

  1. additionUpon completion of addition
  2. stirringthe reaction mixture was stirred for 1.5 hours
  3. additionUpon completion of addition
  4. stirringthe reaction mixture was stirred for one hour
  5. extractionwas extracted with two 50 mL portions of hexane
  6. washThe combined hexane layers were washed with 25 mL of a saturated, aqueous solution of sodium chloride
  7. dry with materialThe organic layer was dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under reduced pressure to a residual oil
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7ad8e9c6d9104a6d81abbd02d40d30cc
Source dataset
uspto-grants-1989_02
Patent number
US04808762

Reaction notes

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