Ethanol → 3-Ethoxycarbonyl-4-hydroxy-1-azabicyclo[3.3.1]non-3-ene

HRID 1813930Notes

Reaction equation

HRID 1813930 reaction equation
C(O[K])(C)(C)C.[CH2:7]([O:9][C:10]([CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][CH2:17][CH:16]([C:20]([O:22]CC)=O)[CH2:15]1)=[O:11])[CH3:8].CCO>C1(C)C=CC=CC=1>[CH2:7]([O:9][C:10]([C:12]1[CH2:13][N:14]2[CH2:15][CH:16]([C:20]=1[OH:22])[CH2:17][CH2:18][CH2:19]2)=[O:11])[CH3:8]

Participants

5

Reactant 3

HCID 702EthanolHCID 115651151-Piperidinepropanoic acid, 3-(ethoxycarbonyl)-, ethyl esterHCID 178418922HCID 178418922, compound

Product 1

HCID 547202243-Ethoxycarbonyl-4-hydroxy-1-azabicyclo[3.3.1]non-3-eneYield 40.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A suspension of tert-BuOK (505 mg, 4.5 mmol) in anhydrous toluene (4.5 mL) was refluxed (1 h) and then an anhydrous toluene solution (1.5 mL) of 15a (386 mg, 1.5 mmol) was added (20 min) and the reaction mixture was refluxed for an additional 3 h, and then cooled. EtOH (2 mL) was added, and the reaction was filtered (Celite pad) and concentrated in vacuo. The residue was purified by PTLC (5% MeOH—CHCl3) to give 4 (127 mg, 40%) as a yellow oil: Rf 0.21 (5% MeOH—CHCl3); IR (neat) 2932, 2857, 1656, 1292, 1207 cm−1; 1H NMR (CDCl3, 500 MHz) δ 1.25 (t, J=7.1 Hz, 3H, CH2CH3), 1.55-1.64 (m, 2H, C(7)H2), 1.65-1.73 (m, 1H), C(6)HH′), 1.84-1.86 (m, 1H, C(6)HH′), 2.19 (br s, 1H, C(5)H), 2.89 (d, J=13.0 Hz, 1H), C(9)HH′), 2.90-2.96 (m, 2H, C(8)H2), 2.96 (d, J=13.0 Hz, 1H, C(9)HH′), 3.24 (d, J=16.8 Hz, 1H, C(2)HH′), 3.73 (d, J=16.8 Hz, 1H, C(2)HH′), 4.17 (q, J=7.1 Hz, 2H, CH2CH3), 11.83 (br s, 1H, C(4)OH), the 1H NMR assignments were consistent with the COSY spectrum; 13C NMR (CDCl3, 150 MHz) 14.2 (CH2CH3), 19.1 (C(7)), 26.6 (C(6)), 32.2 (C(5)), 49.5 (C(2)), 51.4 (C(9)), 55.2 (C(8)), 60.2 (CH2CH3), 99.3 (C(3)), 170.6 (C(O)), 172.1 (C(4) ppm, the assignments were consistent with the DEPT, HMQC and HMBC spectra; MS (+CI) 212 [M+1]+; Mr (+CI) 212.128 08 [M+1]+ (calcd for C11H18NO3 212.128 67). Anal. (C11H17NO3): C, H, N.

Workup

  1. temperaturewas refluxed (1 h)
  2. temperaturethe reaction mixture was refluxed for an additional 3 h
  3. temperaturecooled
  4. filtrationthe reaction was filtered (Celite pad)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by PTLC (5% MeOH—CHCl3)

Sources & evidence

ORD record
ord-ee3f7cfbea43451087acd1c7ecdd6010
Source dataset
uspto-grants-2005_04
Patent number
US06875774B2

Reaction notes

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