Water → 3-(2-Hydroxyethylidene)-8-azabicyclo[3.2.1]octane-8-carboxylic acid t-butyl ester

HRID 1191495Notes

Reaction equation

HRID 1191495 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][C:11](=[CH:16][C:17](OCC)=[O:18])[CH2:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C.C(O)(C)C.O>C1COCC1.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][C:11](=[CH:16][CH2:17][OH:18])[CH2:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 3776IsopropanolHCID 14487Diisobutylaluminum hydrideHCID 58968477Tert-butyl 3-(2-ethoxy-2-oxoethylidene)-8-azabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 689104973-(2-Hydroxyethylidene)-8-azabicyclo[3.2.1]octane-8-carboxylic acid t-butyl esterYield 82.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A reaction flask was charged with 3-ethoxycarbonylmethylene-8-azabicyclo[3.2.1]octane-8-carboxylic acid t-butyl ester (2.70 g, 9.1 mmol) in dry THF (15 mL) under Argon. The solution was cooled to −78° and DIBAL-H (1.5 M in toluene, 13.7 mL, 20.5 mmol) was added dropwise over 20 min. The reaction was stirred at −78° for 1 h then the temperature was raised to rt. The reaction mixture was added i-propanol (5 mL) and stirred at rt for 5 min followed by addition of water (10 mL). DCM was added and the suspension was stirred at rt for 15 min. The suspension was filtered and the collected organic phase was dried over Na2SO4, filtered, and concentrated. The product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 1:1; EtOAc) to give the title compound (1.908 g, 82%). 1H NMR (CDCl3) δ 5.57-5.51 (m, 1H), 4.24-4.17 (m, 2H), 4.36-4.06 (m, 2H), 2.54-2.46 (m, 1H), 2.40-2.34 (m, 1H), 2.24-2.18 (m, 1H), 2.01-1.96 (m, 1H), 1.90-1.78 (m, 3H), 1.60-1.46 (m, 2H), 1.45 (s, 9H).

Workup

  1. temperatureThe solution was cooled to −78°
  2. stirringstirred at rt for 5 min
  3. stirringthe suspension was stirred at rt for 15 min
  4. filtrationThe suspension was filtered
  5. dry with materialthe collected organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 1:1; EtOAc)

Sources & evidence

ORD record
ord-14735d19a4c24e4f824e9abf78eea0f8
Source dataset
uspto-grants-2014_03
Patent number
US08680115B2

Reaction notes

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