HCID 19738107, compound → HCID 19738110, compound

HRID 2255424Notes

Reaction equation

HRID 2255424 reaction equation
[CH3:1][CH:2]1[CH:7]2[CH:8]([CH:10]([CH3:12])[CH3:11])[CH2:9][CH:4]([CH:5]([C:13]([OH:15])=O)[CH2:6]2)[N:3]1[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[CH3:23][Li]>CCOCC>[CH3:1][CH:2]1[CH:7]2[CH:8]([CH:10]([CH3:12])[CH3:11])[CH2:9][CH:4]([CH:5]([C:13](=[O:15])[CH3:23])[CH2:6]2)[N:3]1[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

4

Reactant 2

HCID 19738107HCID 19738107, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 19738110HCID 19738110, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-methyl-8-isopropyl-2-(phenylmethyl)-2-azabicyclo[2.2.2]octane-6-carboxylic acid (30.1 g, 100 mmol) and ether (300 mL) was cooled to 0° C. and methyllithium (330 mL, 1.2N solution in ether) was added dropwise over 2 hours. The mixture was stirred for 1 hour at 0° C. and quenched by the addition of saturated NH4Cl (100 mL). The mixture was poured into water (1 L), and the aqueous layer was separated and extracted with ether (1×200 mL). The ether extracts were combined, washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with 25% ether/hexane to afford 14.3 g (48%) of 1-[3-methyl-8-isopropyl-2-(phenylmethyl)-2-azabicyclo[2.2.2]octan-6-yl]-ethanone. The product was treated with ethereal.HCl to afford 15.2 g of the hydrochloride salt as a white solid, m.p. 208.5°-210° C. (dec.) when recrystallized from ethanol/ether.

Workup

  1. customquenched by the addition of saturated NH4Cl (100 mL)
  2. additionThe mixture was poured into water (1 L)
  3. customthe aqueous layer was separated
  4. extractionextracted with ether (1×200 mL)
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography on silica gel eluting with 25% ether/hexane

Sources & evidence

ORD record
ord-f3053e685ddf4d9ab17ae4de5ae9b56c
Source dataset
uspto-grants-1993_08
Patent number
US05240935

Reaction notes

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