Ammonium Chloride → N-Benzyl-(R)-alpha-methylbenzyl-3(S)-(6-methoxypyridin-3-yl)-beta-alanine ethyl ester

HRID 1108415

Reaction equation

[CH2:1]([NH:8][C@H:9](C)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:17]([Li])CCC.[CH3:22][O:23][C:24]1[N:29]=[CH:28][C:27]([CH:30]=[CH:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:26][CH:25]=1.[NH4+].[Cl-]>C1COCC1.CCCCCC.CCOC(C)=O>[CH2:35]([O:34][C:32](=[O:33])[C@H:31]([CH3:17])[C@@H:30]([C:27]1[CH:28]=[N:29][C:24]([O:23][CH3:22])=[CH:25][CH:26]=1)[N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[CH3:36]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of N-benzyl-(R)-α-methylbenzylamine (97.5 g, 462 mmol) in THF (750 mL) at 0° C. was added n-butyllithium (2.5M in hexanes; 178.5 mL, 446 mmol). The dark violet solution was stirred at 0° C. for 20 minutes, cooled to -78° C. and the ester 19-3 (63.7 g, 308 mmol) in THF (250 mL) was added over 60 minutes. The resulting solution was stirred at -78° C. for 1 hr then cannulated into saturated NH4Cl and extracted with EtOAc, washed with water then brine, dried and concentrated in vacuo to give an oil. Column chromatography (silica gel; hexane/EtOAc, 9:1 then 4:1) gave 19-4 as an oil contaminated with N-benzyl-(R)-α-methylbenzylamine . This oil was taken up in 5% AcOH in water and extracted with diethyl ether (4×). The organic layers were dried over MgSO4 and the solvent removed to give the title compound 19-4.

Workup

temperaturecooled to -78° C.
stirringThe resulting solution was stirred at -78° C. for 1 hr
extractionextracted with EtOAc
washwashed with water
dry with materialbrine, dried
concentrationconcentrated in vacuo
customto give an oil

Sources & evidence

ORD record: ord-6cb64bd668db4dc79209b05ce36fb3ab
Source dataset: uspto-grants-2000_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06066648

Linked notes

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