Ammonium Chloride → Cyclopentyl(2'-fluoro-5'-methoxy-4-((4-methoxybenzyl)oxy)biphenyl-2-yl)methanol

HRID 1049592Notes

Reaction equation

HRID 1049592 reaction equation
[Cl-].[Li+].C[Si](C[Mg]Cl)(C)C.[CH:10]1([Mg]Br)[CH2:14][CH2:13][CH2:12][CH2:11]1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=1[C:26]1[C:27]([CH:42]=[O:43])=[CH:28][C:29]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)=[CH:30][CH:31]=1.[Cl-].[NH4+]>C(OCC)C.C1COCC1.[Cl-].[Zn+2].[Cl-]>[CH:10]1([CH:42]([C:27]2[CH:28]=[C:29]([O:32][CH2:33][C:34]3[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=3)[CH:30]=[CH:31][C:26]=2[C:19]2[CH:20]=[C:21]([O:24][CH3:25])[CH:22]=[CH:23][C:18]=2[F:17])[OH:43])[CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 433294Lithium ChlorideHCID 1177599142'-Fluoro-5'-methoxy-4-((4-methoxybenzyl)oxy)biphenyl-2-carbaldehydeHCID 178418680HCID 178418680, compoundHCID 178419650HCID 178419650, compound

Product 1

HCID 117759597Cyclopentyl(2'-fluoro-5'-methoxy-4-((4-methoxybenzyl)oxy)biphenyl-2-yl)methanol

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a mixture of zinc chloride (34 mg), lithium chloride (117 mg) and THF (1 mL) was added a solution (1 M, 0.49 mL) of trimethylsilylmethylmagnesium chloride in diethyl ether, and the mixture was stirred at room temperature for 15 min. To the reaction mixture was added a solution (1 M, 2.7 mL) of cyclopentylmagnesium bromide in THF, and the mixture was stirred at room temperature for 45 min. To the reaction mixture was added a solution of 2′-fluoro-5′-methoxy-4-((4-methoxybenzyl)oxy)biphenyl-2-carbaldehyde (301 mg) obtained in Example 93, step 2, in THF (2 mL) at 0° C., and the mixture was stirred at 0° C. for 1 hr. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (40 mg) as a colorless oil.

Workup

  1. stirringthe mixture was stirred at room temperature for 45 min
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-c625d02153de40dfa69701f5e467bf1f
Source dataset
uspto-grants-2016_07
Patent number
US09382188B2

Reaction notes

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