Sodium Hydroxide → 2-[2-[4-[Bis(4-fluorophenyl)methyl]-1-piperidinyl]ethyl]-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepin-5(4H)-one dihydrochloride hemihydrate

HRID 4844

Reaction equation

HRID 4844 reaction equation
[ClH:1].[Cl:2][CH2:3][CH2:4][CH:5]1[CH2:11][N:10]([CH3:12])[C:9](=[O:13])[C:8]2[CH:14]=[CH:15][CH:16]=[N:17][C:7]=2[O:6]1.[OH-].[Na+].[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:23][CH:22]=1>C(Cl)(Cl)Cl>[OH2:6].[ClH:2].[ClH:1].[F:40][C:37]1[CH:38]=[CH:39][C:34]([CH:27]([C:24]2[CH:23]=[CH:22][C:21]([F:20])=[CH:26][CH:25]=2)[CH:28]2[CH2:33][CH2:32][N:31]([CH2:3][CH2:4][CH:5]3[CH2:11][N:10]([CH3:12])[C:9](=[O:13])[C:8]4[CH:14]=[CH:15][CH:16]=[N:17][C:7]=4[O:6]3)[CH2:30][CH2:29]2)=[CH:35][CH:36]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27]([CH:28]2[CH2:29][CH2:30][N:31]([CH2:3][CH2:4][CH:5]3[CH2:11][N:10]([CH3:12])[C:9](=[O:13])[C:8]4[CH:14]=[CH:15][CH:16]=[N:17][C:7]=4[O:6]3)[CH2:32][CH2:33]2)[C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)=[CH:23][CH:22]=1.[ClH:2].[ClH:2]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 132505444-[Bis(4-fluorophenyl)methyl]piperidineHCID 137264372-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepin-5(4H)one hydrochloride

Product 1

HCID 1317147112-[2-[4-[Bis(4-fluorophenyl)methyl]-1-piperidinyl]ethyl]-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepin-5(4H)-one dihydrochloride hemihydrate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Ten grams (0.036 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepin-5-(4H)-one hydrochloride were partitioned between dilute sodium hydroxide and chloroform. The chloroform was dried over sodium sulfate and concentrated on the rotary evaporator. The residue was dissolved in 50 ml of ethanol and 10.3 g (0.036 mole) of 4-[bis(4-fluorophenyl)-methyl]piperidine was added. The solution was heated to reflux for 18 hr and concentrated on the rotary evaporator. The residue was partitioned between dilute sodium hydroxide and chloroform. The chloroform was dried over anhydrous sodium sulfate and concentrated. The residue was chromatographed on a Waters 500 HPlC (silica/92% ethyl acetate-8% triethylamine). After concentration of the desired product, the residue was dissolved in isopropyl alcohol and treated with ethereal hydrogen chloride. The resulting crystals weighed 3 g (14%) and melted at 160°-180° C.

Workup

  1. dry with materialThe chloroform was dried over sodium sulfate
  2. concentrationconcentrated on the rotary evaporator
  3. dissolutionThe residue was dissolved in 50 ml of ethanol
  4. temperatureThe solution was heated
  5. temperatureto reflux for 18 hr
  6. concentrationconcentrated on the rotary evaporator
  7. customThe residue was partitioned between dilute sodium hydroxide and chloroform
  8. dry with materialThe chloroform was dried over anhydrous sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was chromatographed on a Waters 500 HPlC (silica/92% ethyl acetate-8% triethylamine)
  11. dissolutionAfter concentration of the desired product, the residue was dissolved in isopropyl alcohol
  12. additiontreated with ethereal hydrogen chloride

Sources & evidence

ORD record
ord-689206cad7fa430599e0f8db786a2e2d
Source dataset
uspto-grants-1988_02
Patent number
US04727152

Linked notes

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