Hydrochloric Acid → HCID 19829444, compound

HRID 1493873Notes

Reaction equation

HRID 1493873 reaction equation
Br[CH2:2][CH2:3][CH:4]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[O:7][CH2:6][CH2:5]1.[ClH:14].[NH:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:22](=[O:30])[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:17][CH2:16]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl>CC(=O)CC.CC(C)=O.C(O)(C)C>[ClH:14].[O:7]1[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[CH:4]([CH2:3][CH2:2][N:15]2[CH2:16][CH2:17][CH:18]([NH:21][C:22](=[O:30])[C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[CH2:19][CH2:20]2)[CH2:5][CH2:6]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 143302824-(2-bromoethyl)-3,4-dihydro-2H-benzopyranHCID 19829414Benzamide, 4-fluoro-N-4-piperidinyl-, hydrochloride (1:1)

Product 1

HCID 19829444HCID 19829444, compoundYield 63.3%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 3776IsopropanolSolventHCID 6569Methyl Ethyl KetoneSolvent

Procedure

The procedure is as in Example 4, but starting with 4-(2-bromoethyl)-3,4-dihydro-2H-benzopyran (1.9 g), N-(4-piperidyl)-4-fluorobenzamide hydrochloride (2 g), dry potassium carbonate (2.15 g) and potassium iodide (0.95 g) in 2-butanone (60 cc). The yellow oil obtained is purified by chromatography on a column 4 cm in diameter containing a silica gel (110 g), eluting with a toluene/diethylamine/ethanol mixture (60:20:20 by volume) (300 cc) and collecting 30-cc fractions. The fractions between 330 and 900 cc are concentrated to dryness. The yellow crystals obtained are dissolved in acetone (25 cc) and treated with a 3.4N solution (3 cc) of hydrochloric acid in isopropanol. The precipitate formed is filtered off on sintered glass and then recrystallized in an ethanol/acetone mixture (20:60 by volume) (80 cc). After the addition of ethyl ether (10 cc), N-{1-[2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4-piperidyl}-4-fluorobenzamide hydrochloride (2.05 g) is obtained in the form of a crystalline white solid, m.p. 240° C.

Workup

  1. customThe yellow oil obtained
  2. customis purified by chromatography on a column 4 cm in diameter
  3. additioncontaining a silica gel (110 g)
  4. washeluting with a toluene/diethylamine/ethanol mixture (60:20:20 by volume) (300 cc)
  5. customcollecting 30-cc fractions
  6. concentrationThe fractions between 330 and 900 cc are concentrated to dryness
  7. customThe yellow crystals obtained
  8. customThe precipitate formed
  9. filtrationis filtered off on sintered glass
  10. customrecrystallized in an ethanol/acetone mixture (20:60 by volume) (80 cc)
  11. additionAfter the addition of ethyl ether (10 cc)

Sources & evidence

ORD record
ord-b6992bca6f8247e4894f784274d32a19
Source dataset
uspto-grants-1991_06
Patent number
US05025013

Reaction notes

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