Acetic Acid → HCID 57076656, compound

HRID 275198Notes

Reaction equation

HRID 275198 reaction equation
[C:1]([OH:4])(=[O:3])[CH3:2].C(=O)C.C([BH3-])#N.[Na+].Cl.C(=O)([O-])[O-].[K+].[K+].[CH2:19]([N:26]1[CH2:31][CH:30]2[C:28]([CH2:32][NH:33][CH2:34]C)([CH2:29]2)[CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.N[CH2:37][C:38]12C[CH:42]1CN(CC1C=CC=CC=1)[CH2:39]2.C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>CO.O.C(Cl)Cl.O1CCOCC1>[CH2:19]([N:26]1[CH2:31][CH:30]2[C:28]([CH2:32][NH:33][CH2:34][CH2:2][C:1]([O:4][C:38]([CH3:42])([CH3:39])[CH3:37])=[O:3])([CH2:29]2)[CH2:27]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

14

Reactant 9

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 90495Di-tert-butyl dicarbonateHCID 5003444Sodium cyanoborohydrideHCID 157134241-(3-Benzyl-3-azabicyclo[3.1.0]hexan-1-yl)methanamineHCID 20089991HCID 20089991, compound

Product 1

HCID 57076656HCID 57076656, compoundYield 16%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

The compound of Preparation A.4. (1.1 g, 5.4 mmol) was dissolved in methanol (55 ml) and treated with acetic acid (0.31 ml, 5.4 mmol), acetaldehyde (0.30 ml, 5.4 mmol) and sodium cyanoborohydride (341 mg, 5.4 mmol). The reaction mixture was allowed to stir at room temperature for 18 hours; it was then diluted with water and methylene chloride and acidified to pH 1 with 6N hydrochloric acid. Potassium carbonate was then added until the pH of the aqueous layer was 10; the mixture was extracted three times with methylene chloride, and the combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was subjected to silica gel chromatography (eluant: 89:10:1 chloroform:methanol:concentrated ammonium hydroxide) to provide a colorless oil (390 mg, 2:1 mixture of 3-benzyl-1-ethylaminomethyl-3-azabicyclo[3.1.0]hexane and 1-aminomethyl-3-benzyl-3-azabicyclo[3.1.0]hexane). This material was dissolved in dioxane (18 ml) and water (2 ml and treated with triethylamine (0.7 ml, 5.0 mmol) and di-tert-butyl dicarbonate (1.1 g, 5.0 mmol); the reaction mixture was allowed to stir for 18 hours at room temperature. The solution was partitioned between methylene chloride and saturated aqueous sodium bicarbonate. The aqueous layer was extracted three times with methylene chloride and the combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting colorless oil was subjected to purification on a Chromatotron (trademark) (eluant: 400:10:1 chloroform:methanol:concentrated ammonium hydroxide) to provide the title product as a yellow oil (277 mg, 0.84 mmol, 16% yield). 1H NMR (CDCl3): 7.30 (m, 5H), 3.65 (bs, 2H), 3.30 (m, 4H), 3.00 (m, 2H), 2.44 (m, 2H), 1.48 (s, 9H), 1.25 (m, 1H), 1.15 (m, 1H), 1.12 (t, J=7 Hz, 3H), 0.46 (bs, 1H).

Workup

  1. customThe compound of Preparation A.4
  2. extractionthe mixture was extracted three times with methylene chloride
  3. dry with materialthe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide
  7. stirringto stir for 18 hours at room temperature
  8. customThe solution was partitioned between methylene chloride and saturated aqueous sodium bicarbonate
  9. extractionThe aqueous layer was extracted three times with methylene chloride
  10. dry with materialthe combined organic layers were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe resulting colorless oil was subjected to purification on a Chromatotron (trademark) (eluant: 400:10:1 chloroform:methanol:concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-f6afece454d441ae931d7a852a59bcd4
Source dataset
uspto-grants-1995_02
Patent number
US05391763

Reaction notes

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