o-Xylyl bromide → 1-(1,1-Dimethylethyl) 4-methyl 4-[(2-methylphenyl)methyl]-1,4-piperidinedicarboxylate

HRID 1068399Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:17])[CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[Li+].CC([N-]C(C)C)C.[CH3:26][C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH2:29]Br>C1COCC1>[CH3:1][O:2][C:3](=[O:17])[C:4]1([CH2:26][C:27]2[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=2[CH3:29])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[CH2:6][CH2:5]1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of N-t-butoxycarbonyl isonipecotic acid methyl ester (10.1 g 41.8 mmol) in 140 ml of dry THF at −78° C. was added LDA (59 ml of a 1.0 M solution in THF, 59 mmol) over 15 min. The resulting orange solution was stirred at −78° C. for 1 hr and then treated dropwise with 2-methylbenzyl bromide (6.80 ml, 50.7 mmol) and then allowed to warm slowly to room temperature over 16 hrs. The reaction was quenched with saturated aqueous NH4Cl, diluted with H2O, and extracted with EtOAc. The combined organic extracts were washed with brine, and concentrated in vacuo to an orange gum. Chromatography (SiO2, eluting with 20 to 30% EtOAc in hexanes) and evaporation of solvent in vacuo, afforded the product as a white solid.

Workup

temperatureto warm slowly to room temperature over 16 hrs
customThe reaction was quenched with saturated aqueous NH4Cl
additiondiluted with H2O
extractionextracted with EtOAc
washThe combined organic extracts were washed with brine
concentrationconcentrated in vacuo to an orange gum
washChromatography (SiO2, eluting with 20 to 30% EtOAc in hexanes) and evaporation of solvent in vacuo

Sources & evidence

ORD record: ord-9e56cbc6413c46738f4cae43860eee18
Source dataset: uspto-grants-2001_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06248756B1

Reaction notes

Loading…