Hydrochloric Acid → HCID 67896137, compound

HRID 981970Notes

Reaction equation

HRID 981970 reaction equation
C([BH3-])#N.[Na+].[C:5]1([CH2:11][N:12]2[CH2:17][CH2:16][C:15](=O)[CH:14]([O:19][CH3:20])[CH2:13]2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[NH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Cl>CO>[C:5]1([CH2:11][N:12]2[CH2:17][CH2:16][C@H:15]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C@H:14]([O:19][CH3:20])[CH2:13]2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6115AnilineHCID 5003444Sodium cyanoborohydrideHCID 15078438HCID 15078438, compound

Product 1

HCID 67896137HCID 67896137, compoundYield 3.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Sodium cyanoborohydride (0.17 g, 27 mmol) and 5.2 g of 3A molecular sieves were slowly added at room temperature to a stirred solution of 1-phenylmethyl-3-methoxy-4-piperidone (5b, 1 g, 4.56 mmol) from Example 3 in 40 ml of methanol, 2.55 g (27 mmol) of aniline and 3.57 ml of 2.55N hydrochloric acid in methanol. The reaction mixture was stirred at room temperature for 3 days, after which time the molecular sieves were filtered off and the solution was made acidic with 10ml of 10% hydrochloric acid. The methanol was evaporated under vacuum and the residue was diluted with 20 ml of water, then extracted with ether (50 ml). The aqueous layer was then made alkaline with 10% sodium hydroxide (solution and extracted with 3×100 ml of ether. The combined organic layers were dried, then concentrated under vacuum and purified by column chromatography (silica gel; ethyl acetate/hexane; 1:1) to yield the intermediates cis-1-phenylmethyl-3-methoxy-4-phenylaminopiperidine (7b, 0.52 g, 38.23%) and trans-1-phenylmethyl-3-methoxy-4-phenylaminopiperidine (7b, 0.05 g, 3.7%).

Workup

  1. filtrationafter which time the molecular sieves were filtered off
  2. customThe methanol was evaporated under vacuum
  3. additionthe residue was diluted with 20 ml of water
  4. extractionextracted with ether (50 ml)
  5. extractionextracted with 3×100 ml of ether
  6. customThe combined organic layers were dried
  7. concentrationconcentrated under vacuum
  8. custompurified by column chromatography (silica gel; ethyl acetate/hexane; 1:1)

Sources & evidence

ORD record
ord-c867d9fbea5447b4afd119fd3ebdcea1
Source dataset
uspto-grants-1991_02
Patent number
US04994471

Reaction notes

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