1-azabicyclo[3.2.1]octan-6-one → HCID 57548064, compound

HRID 2043056Notes

Reaction equation

HRID 2043056 reaction equation
C([CH:3](CC)[C:4](O)=[O:5])C.[CH:9](=[O:12])[C:10]#[CH:11].[CH3:13][C:14]([O-])(C)C.[K+].[N:19]12[CH2:27][CH:23]([C:24](=[O:26])[CH2:25]1)[CH2:22][CH2:21][CH2:20]2>C1COCC1>[CH2:13]([O:12][CH:9]([O:5][CH2:4][CH3:3])[C:10]#[C:11][C:24]1([OH:26])[CH2:25][N:19]2[CH2:27][CH:23]1[CH2:22][CH2:21][CH2:20]2)[CH3:14]

Participants

5

Reactant 3

HCID 4183471-azabicyclo[3.2.1]octan-6-oneHCID 23665647Potassium tert-butoxideHCID 87338581HCID 87338581, compound

Product 1

HCID 57548064HCID 57548064, compoundYield 86.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

A suspension of propargylaldehyde diethyl acetate (14.62 g, 114 mmol) and t-BuOK (14.92 g, 133 mmol) in 350 ml of anhydrous THF was stirred for 1 hour at −10° C. under N2. Then a suspension of 1-aza-bicyclo[3.2.1]octan-6-one (53, J. Med. Chem., 36, 1993, 683-689) (11.92 g, 95 mmol) in 100 ml of THF was added and the resulting homogeneous reaction mixture was stirred for another 2 hours at 0° C. Then the mixture was quenched with an aqueous acetic acid solution at 0° C. and concentrated in vacuo. Ethyl acetate was added and the organic layer was washed with 2 N NaOH, dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash chromatography (dichloromethane/MeOH/NH4OH 93/7/0.5) afforded 6-(3,3-diethoxy-prop-1-ynyl)-1-azabicyclo[3.2.1]octan-6-ol (54) as an oil (20.87 g, 86%). LCMS (Method A): Rt: 1.18 min, ([M+H]+=254). 1H-NMR (400 MHz, CDCl3) δ 5.28 (s, 1H), 3.74-3.65 (m, 2H), 3.61-3.52 (m, 2H), 3.45 (d, J=13 Hz, 1H), 3.12-3.04 (m, 1H), 3.0-2.82 (m, 4H), 2.22-2.18 (m, 1H), 2.17-2.02 (m, 1H), 1.98-1.89 (m, 1H), 1.71-1.61 (m, 1H), 1.39-1.30 (m, 1H), 1.22 (t, J=7 Hz, 6H).

Workup

  1. additionwas added
  2. stirringthe resulting homogeneous reaction mixture was stirred for another 2 hours at 0° C
  3. customThen the mixture was quenched with an aqueous acetic acid solution at 0° C.
  4. concentrationconcentrated in vacuo
  5. additionEthyl acetate was added
  6. washthe organic layer was washed with 2 N NaOH
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by flash chromatography (dichloromethane/MeOH/NH4OH 93/7/0.5)

Sources & evidence

ORD record
ord-8c7884de223c49eabbf05225690fcd42
Source dataset
uspto-grants-2013_11
Patent number
US08586606B2

Reaction notes

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