Hydrochloric Acid → HCID 66608287, compound

HRID 218980Notes

Reaction equation

HRID 218980 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([CH:8](Cl)[C:9]2[S:10][C:11]3[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=3[CH:13]=2)[CH:7]=1.[BH4-].[Na+].[OH-].[Na+].Cl>O.C1(C)C=CC=CC=1.O1CCOCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([CH:7]=1)[CH2:8][C:9]1[S:10][C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[CH:13]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 249881712-((5-Bromo-2-fluorophenyl)chloromethyl)benzo(b)thiophene

Product 1

HCID 66608287HCID 66608287, compoundYield 75%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
56 °C

Procedure

A dioxane (1.1 liters) solution of 2-[(5-bromo-2-fluorophenyl)(chloro)methyl]-1-benzothiophene (551 g) was added to a dioxane (3.3 liters)-water (1.6 liters) solution of sodium borohydride (410 g) and sodium hydroxide (31 g) at 60 to 66° C., followed by stirring at 52 to 60° C. for 39 hours. To the reaction mixture was added toluene (5.5 liter), water (3.8 liters) and 36% hydrochloric acid (620 ml) to conduct extraction. The organic layer was subjected to distillation under reduced pressure to distil off the solvent. The residue was dried under reduced pressure. The obtained crystals were dissolved in 2-propanol (1 liter) and methanol (1 liter) with heating, followed by stirring at 0° C. for 20.5 hours. The separated-out crystals were collected by filtration, washed with methanol (500 ml), and dried under reduced pressure to obtain 2-(5-bromo-2-fluorobenzyl)-1-benzothiophene [373 g, yield: 75.0%, purity: 99% (HPLC)] as white crystals. Incidentally, the 2-[(5-bromo-2-fluorophenyl)(chloro)methyl]-1-benzothiophene is the same as the compound (5) obtained in the second step of the production method of the present invention.

Workup

  1. extractionextraction
  2. distillationThe organic layer was subjected to distillation under reduced pressure
  3. customto distil off the solvent
  4. customThe residue was dried under reduced pressure
  5. dissolutionThe obtained crystals were dissolved in 2-propanol (1 liter)
  6. temperaturemethanol (1 liter) with heating
  7. stirringby stirring at 0° C. for 20.5 hours
  8. filtrationThe separated-out crystals were collected by filtration
  9. washwashed with methanol (500 ml)
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-7750ffc502b844f8a9ef56c2ff104d50
Source dataset
uspto-grants-2012_06
Patent number
US08198464B2

Reaction notes

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