Ammonia → HCID 22116561, compound

HRID 1276629Notes

Reaction equation

HRID 1276629 reaction equation
[CH:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[CH:6]([CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][C:22]4([C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[C:26](=O)[O:25]4)[CH:21]([CH3:34])[CH2:20]3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.B.C1COCC1.[ClH:41].N>O1CCCC1>[ClH:41].[CH:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[CH:6]([CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][C:22]4([C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[CH2:26][O:25]4)[CH:21]([CH3:34])[CH2:20]3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 2723981Borane;tetrahydrofuranHCID 22116567HCID 22116567, compound

Product 1

HCID 22116561HCID 22116561, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(1RS,3'SR)-1'-[3-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)-propyl]3'-methyl-spiro[isobenzofuran-1,4'-piperidin]-3-one (0.5 mmol) was dissolved in tetrahydrofurane and borane-THF-complex (1M solution in THF, 3 mmol) was added under argon. The resulting mixture was heated at reflux for 18 h. It was cooled to 0° C., and 1M HCl was added dropwise until no more gas evolution was observed. The mixture was concentrated in vacuo and HCl (1N, 5 ml) was added to the white foam obtained, and the resulting mixture was stired at 100° C. for 1 h. The solution was then cooled and basified with concentrated aqueous ammonia solution. The product was extracted into dichloromethane and purified by column chromatography over silicagel (ethylacetate). Addition of HCl in ethanol to a solution of the product in ethylacetate/ethanol yielded (1RS,3'SR)-1'-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)-propyl]-3'-methyl-spiro[isobenzofuran-1,4'-piperidine] hydrochloride (0.18 g, 82%) as colorless solid, m.p. 225° C. and MS: m/e=438.4 (M+H+).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 18 h
  3. concentrationThe mixture was concentrated in vacuo and HCl (1N, 5 ml)
  4. additionwas added to the white foam
  5. customobtained
  6. temperatureThe solution was then cooled
  7. extractionThe product was extracted into dichloromethane
  8. custompurified by column chromatography over silicagel (ethylacetate)
  9. additionAddition of HCl in ethanol to a solution of the product in ethylacetate/ethanol

Sources & evidence

ORD record
ord-fddba5774436460586648f22e54a4117
Source dataset
uspto-grants-2000_12
Patent number
US06166209

Reaction notes

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