Benzylamine → HCID 86680026, compound

HRID 1915818Notes

Reaction equation

HRID 1915818 reaction equation
[N:1]([C:4]1([CH3:11])[CH:9]([OH:10])[CH2:8][CH:7]=[CH:6][CH2:5]1)=[N+:2]=[N-:3].[CH2:12]([NH2:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[BH3-]C#N.[Na+]>CO.C(Cl)Cl.CO>[N:1]([C:4]1([CH3:11])[CH2:5][CH2:6][N:19]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:7][CH2:8][CH:9]1[OH:10])=[N+:2]=[N-:3]

Participants

6

Reactant 3

HCID 7504BenzylamineHCID 5003444Sodium cyanoborohydrideHCID 86680027HCID 86680027, compound

Product 1

HCID 86680026HCID 86680026, compoundYield 73.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of 6-azido-6-methylcyclohex-3-enol (3.9 g, 25 mmol) in MeOH/DCM (100 mL/20 mL) cooled to −78° C. was degassed by bubbling nitrogen through it for 5 min. Ozone was then bubbled through the reaction mixture until a greyish-blue colour persisted. Nitrogen was again bubbled through the cold reaction mixture until only a pale colour persisted. A solution of benzylamine (2.7 g, 25 mmol) dissolved in MeOH (5 mL) was added followed by NaCNBH3 (6.4 g, 101.5 mmol) in MeOH (10 mL). The mixture was allowed to warm to room temperature and stirred for 16 hr. The solvents were removed under reduced pressure and the residue partitioned between EtOAc (50 mL) and water (50 mL). The aqueous layer was further extracted with EtOAc (3×50 mL) and the combined organic layers were washed with brine (40 mL), separated, dried over MgSO4 and concentrated under reduced pressure. Purification of the residue via silica gel column chromatography (1-10% 7 M NH3 in MeOH/DCM) gave 5-azido-1-benzyl-5-methylazepan-4-ol as a viscous yellow oil (4.8 g, 73%). 1H NMR (400 MHz, CDCl3) δ 7.25-7.34 (m, 5H), 3.69-3.62 (m, 2H), 3.51-3.47 (m, 2H), 2.96-2.89 (m, 1H), 2.69-2.62 (m, 3H), 2.19-2.11 (m, 1H), 1.99-1.85 (m, 1H), 1.78-1.68 (m, 1H), 1.61-1.57 (m, 1H), 1.43 (s, 3H).

Workup

  1. customwas degassed
  2. customby bubbling nitrogen through it for 5 min
  3. customOzone was then bubbled through the reaction mixture until a greyish-blue colour
  4. customNitrogen was again bubbled through the cold reaction mixture until only a pale colour
  5. additionwas added
  6. customThe solvents were removed under reduced pressure
  7. customthe residue partitioned between EtOAc (50 mL) and water (50 mL)
  8. extractionThe aqueous layer was further extracted with EtOAc (3×50 mL)
  9. washthe combined organic layers were washed with brine (40 mL)
  10. customseparated
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated under reduced pressure
  13. customPurification of the residue via silica gel column chromatography (1-10% 7 M NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-6296954b3a564b6fb437f520f095f24c
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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