Methanol → HCID 68312803, compound

HRID 1530384Notes

Reaction equation

HRID 1530384 reaction equation
Cl.[CH2:2]([N:9]1[CH2:15][CH2:14][CH2:13][CH:12]([CH:16]=[O:17])[CH2:11][CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:18][Mg]Br.CO>C1COCC1>[CH2:2]([N:9]1[CH2:15][CH2:14][CH2:13][CH:12]([CH:16]([OH:17])[CH3:18])[CH2:11][CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 71779147HCID 71779147, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 68312803HCID 68312803, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cooled suspension of 1-benzylazepane-4-carbaldehyde hydrochloride (1.0 g, 3.95 mmol) in THF (15 mL) was added methylmagnesium bromide (3M in diethyl ether, 4 mL) dropwise. The mixture was slowly warmed to RT and then stirred for 18 h at RT. MeOH was then added and volatiles were removed in vacuo. The resulting residue was dissolved in DMF and filtered thought a pad of silica eluting with 10% 2M NH3/MeOH in DCM. The residue was further purified by column chromatography (Si-PCC, gradient 0-10% 2M NH3/MeOH in DCM) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo affording 1-(1-Benzylazepan-4-yl)ethanol (600 mg, 65%). 1H NMR (CDCl3, 400 MHz): δ 7.38-7.19 (5H, m), 3.99-3.47 (5H, m), 2.92-2.38 (4H, m), 2.01-1.51 (6H, m), 1.19 (3H, m)

Workup

  1. customvolatiles were removed in vacuo
  2. dissolutionThe resulting residue was dissolved in DMF
  3. filtrationfiltered
  4. customThe residue was further purified by column chromatography (Si-PCC, gradient 0-10% 2M NH3/MeOH in DCM)
  5. washThe cartridge was washed with MeOH
  6. washthe product eluted with 2M NH3/MeOH
  7. additionThe product containing fractions
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-aa2fe6a3ca1c4217af744d7bea255665
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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