Acetic Acid → HCID 178420786, compound

HRID 1821164Notes

Reaction equation

HRID 1821164 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.[N:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH:11]2[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]2)[CH:6]=1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[CH:1]1([NH:4][C@H:14]2[CH2:15][CH2:16][C@H:11]([C:7]3[CH:6]=[N:5][CH:10]=[CH:9][CH:8]=3)[CH2:12][CH2:13]2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 69828CyclopropylamineHCID 5049666Sodium triacetoxyborohydrideHCID 200349074-(Pyridin-3-yl)cyclohexan-1-one

Product 1

HCID 178420786HCID 178420786, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

Cyclopropyl amine (11.4 mL, 165 mmol) was added to a solution of 4-(3-pyridyl)cyclohexanone (19.2 g, 110 mmol) in DCE (360 mL) and acetic acid (12.6 mL, 220 mmol). The reaction mixture was cooled to 0° C. and NaBH(OAc)3 (46 g, 220 mmol) was added protionwise. After being stirred for 21 h at 23° C., the reaction was re-cooled to 0° C. and quenched with 1 M NaOH (200 mL). The aqueous layer was extracted with CH2Cl2 (2×200 mL) and the combined organic layers were washed with brine (300 mL), dried with MgSO4, filtered, and concentrated in vacuo. The crude mixture of cis and trans amines was purified by flash column chromatography (gradient elution, 40% EtOAc/hexanes (2.5% TEA)→70% EtOAc/hexanes (2.5% TEA)) to provide trans-N-cyclopropyl-4-(pyridine-3-yl)cyclohexylamine.

Workup

  1. temperaturethe reaction was re-cooled to 0° C.
  2. customquenched with 1 M NaOH (200 mL)
  3. extractionThe aqueous layer was extracted with CH2Cl2 (2×200 mL)
  4. washthe combined organic layers were washed with brine (300 mL)
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. additionThe crude mixture of cis and trans amines
  9. customwas purified by flash column chromatography (gradient elution, 40% EtOAc/hexanes (2.5% TEA)→70% EtOAc/hexanes (2.5% TEA))

Sources & evidence

ORD record
ord-700976556011479281724f92a3158f08
Source dataset
uspto-grants-2009_10
Patent number
US07605289B2

Reaction notes

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