Acetic Acid → Racemic cis benzyl-(6-methyl-spiro[2.5]oct-5-yl)-amine

HRID 905945Notes

Reaction equation

HRID 905945 reaction equation
[CH3:1][CH:2]1[CH2:9][CH2:8][C:5]2([CH2:7][CH2:6]2)[CH2:4][C:3]1=O.[CH2:11]([NH2:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C1C=CC=CC=1.C(Cl)Cl.O>[CH2:11]([NH:18][C@H:3]1[C@@H:2]([CH3:1])[CH2:9][CH2:8][C:5]2([CH2:7][CH2:6]2)[CH2:4]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 7504BenzylamineHCID 5049666Sodium triacetoxyborohydrideHCID 673857556-Methylspiro[2.5]octan-5-one

Product 1

HCID 131729155Racemic cis benzyl-(6-methyl-spiro[2.5]oct-5-yl)-amineYield 60.3%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Racemic 6-methyl-spiro[2.5]octan-5-one (0.92 g, 6.656 mmol) and benzylamine (0.76 mL, 6.989 mmol) were dissolved in benzene (6 mL) and stirred at reflux with continuous removal of H2O for 3 hours. The reaction mixture was allowed to cool to RT and was diluted with DCM (30 mL). The yellow solution was cooled to 0° C. Sodium triacetoxyborohydride (95%, 1.78 g, 7.988 mmol) and acetic acid (0.5 mL, 8.65 mmol) were added. After about 20 minutes, the ice bath was removed and the suspension stirred at RT overnight. The reaction mixture was cooled to 0° C. and quenched by addition of saturated aqueous NaHCO3. The layers were separated and the aqueous layer was extracted with DCM. The combined organic layers were washed once more with saturated aqueous NaHCO3, dried (Na2SO4), filtered and evaporated. The remaining yellow oil was purified by SiO2 chromatography (100 g SiO2, DCM/(DCM:MeOH:NH4OH 60:10:1) 100 to 85% DCM) to give 0.92 g of racemic cis benzyl-(6-methyl-spiro[2.5]oct-5-yl)-amine as a light brown oil (yield 60%).

Workup

  1. temperatureThe yellow solution was cooled to 0° C
  2. customthe ice bath was removed
  3. stirringthe suspension stirred at RT overnight
  4. temperatureThe reaction mixture was cooled to 0° C.
  5. customquenched by addition of saturated aqueous NaHCO3
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with DCM
  8. washThe combined organic layers were washed once more with saturated aqueous NaHCO3
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated
  12. customThe remaining yellow oil was purified by SiO2 chromatography (100 g SiO2, DCM/(DCM:MeOH:NH4OH 60:10:1) 100 to 85% DCM)

Sources & evidence

ORD record
ord-48bd05b16be24039ae3217fdcc9addd3
Source dataset
uspto-grants-2011_09
Patent number
US08012974B2

Reaction notes

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