1-Bromo-3-chloropropane → HCID 15087807, compound

HRID 1638628Notes

Reaction equation

HRID 1638628 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[OH:9])=[CH:4][CH:3]=1.[OH-].[Na+].Br[CH2:19][CH2:20][CH2:21][Cl:22]>[Cl-].C([N+](CC)(CC)CC1C=CC=CC=1)C.CC1C=CC=CC=1>[Cl:22][CH2:21][CH2:20][CH2:19][O:9][CH:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1.[ClH:22].[Cl:22][CH2:21][CH2:20][CH2:19][O:9][CH:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1

Participants

7

Reactant 3

HCID 80061-Bromo-3-chloropropane2×HCID 14798Sodium HydroxideHCID 11264150HCID 11264150, compound

Product 2

HCID 15087807HCID 15087807, compoundYield 55%HCID 19828454HCID 19828454, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 1140TolueneSolvent

Procedure

To a stirred and heated (50° C.) mixture of 15 parts of α-(4-fluorophenyl)-3-pyridinemethanol, 3.4 parts of N,N,N-triethylbenzenemethanaminium chloride, 50 parts of a sodium hydroxide solution 50% and 135 parts of methylbenzene were added dropwise 10 parts of 1-bromo-3-chloropropane. Upon complete addition, stirring was continued for 4 hours. Another portion of 5 parts of 1-bromo-3-chloropropane were added and the whole was stirred for 4 hours at 50° C. After cooling to room temperature, the reaction mixture was poured into ice water and the product was extracted twice with methylbenzene. The combined extracts were washed with a sodium carbonate solution, dried, filtered and evaporated. The excess of 1-bromo-3-chloropropane was distilled off at on oil pump. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (97:3 by volume) as eluent. The pure fractions were collected and the eluent was evaporated, yielding 6 parts (34.3 %) of a mixture of 55% of 3-[(3-chloropropoxy)(4-fluorophenyl)methyl]pyridine and 45% of 3-[(3-chloropropoxy)(4-fluorophenyl)methyl]pyridine monohydrochloride as a residue (int. 64).

Workup

  1. temperatureheated
  2. additionUpon complete addition
  3. stirringstirring
  4. stirringthe whole was stirred for 4 hours at 50° C
  5. extractionthe product was extracted twice with methylbenzene
  6. washThe combined extracts were washed with a sodium carbonate solution
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. distillationThe excess of 1-bromo-3-chloropropane was distilled off at on oil pump
  11. customThe residue was purified by column chromatography over silica gel using
  12. additiona mixture of trichloromethane and methanol
  13. customThe pure fractions were collected
  14. customthe eluent was evaporated

Sources & evidence

ORD record
ord-c8f11cab8c704dc295f1c984afeb1ad2
Source dataset
uspto-grants-1989_11
Patent number
US04880808

Reaction notes

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