Hydrochloric Acid → 1-Benzyl-3-(3,5-difluorophenyl)-3-methoxypyrrolidine

HRID 1188196Notes

Reaction equation

HRID 1188196 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2([O:14][CH3:15])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[H-].[Na+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.Cl>CN(C)C=O>[CH2:18]([N:11]1[CH2:12][CH2:13][C:9]([C:4]2[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=2)([O:14][CH3:15])[CH2:10]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 199358743-(3,5-Difluorophenyl)-3-methoxypyrrolidine

Product 1

HCID 199358491-Benzyl-3-(3,5-difluorophenyl)-3-methoxypyrrolidineYield 62.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-(3,5-difluorophenyl)-3-methoxypyrrolidine (1.3 g, 6.1 mmol) in dry dimethyl formamide (5 mL), was added sodium hydride (60% dispersion in mineral oil, 0.27 g, 6.7 mmol). The mixture was stirred for 15 min after which a solution of benzylbromide (0.725 mL, 6.1 mmol) in dry dimethyl formamide (5 mL) was added dropwise. The mixture was stirred for 30 min, hydrochloric acid (10%, 50 ml) was added and the aqueous phase was extracted with diethylether (50 mL), the aqueous phase was made basic with Na2CO3 and extracted with ethyl acetate (3×50 mL). The combined organic phase was washed with aqueous LiCl (5%, 50 mL), dried (Na2SO4), filtered and evaporated. Purification by flash column chromatography on silica gel (ethyl acetate) gave the title compound (1.15 g, 62%). MS m/z (rel. intensity, 70 eV) 273 (10), 133 (42), 132 (23), 91 (bp), 65 (11).

Workup

  1. additionwas added dropwise
  2. extractionthe aqueous phase was extracted with diethylether (50 mL)
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined organic phase was washed with aqueous LiCl (5%, 50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by flash column chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-c499372152fa475887f6f1b646ff0422
Source dataset
uspto-grants-2014_03
Patent number
US08673962B2

Reaction notes

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