Diisopropylamine → 3-(2-Chloropyridin-3-yl)-3-hydroxypropanoic acid ethyl ester

HRID 1481321Notes

Reaction equation

C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][CH2:14][O:15][C:16]([CH3:18])=[O:17].[Cl:19][C:20]1[C:25]([CH:26]=[O:27])=[CH:24][CH:23]=[CH:22][N:21]=1>C1COCC1>[CH2:14]([O:15][C:16](=[O:17])[CH2:18][CH:26]([C:25]1[C:20]([Cl:19])=[N:21][CH:22]=[CH:23][CH:24]=1)[OH:27])[CH3:13]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 14.5 mL diisopropylamine in 336 mL THF was added 49 mL n-BuLi (2.5 M in hexanes) at 0° C. The mixture was stirred at 0° C. for 15 min, cooled to −78° C. before 10 mL EtOAc were dropwise added. After another 30 min, a solution of 2-chloro-3-pyridine carboxaldehyde (84.8 mmol), dissolved in 84 mL THF, was added. The mixture was stirred at −78° C. for 30 min and then allowed to warm to RT. After stirring for 1.5 h, the reaction was quenched with sat. aq. NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification with CC (KP-SIL™ from Biotage) using Hept/EtOAc (10/1) to EtOAc gives the desired compound as yellow oil.

Workup

additionwere dropwise added
waitAfter another 30 min
additionwas added
stirringThe mixture was stirred at −78° C. for 30 min
temperatureto warm to RT
stirringAfter stirring for 1.5 h
customthe reaction was quenched with sat. aq. NaHCO3 solution
extractionextracted with EtOAc
washThe combined organic layers were washed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customPurification with CC (KP-SIL™ from Biotage)

Sources & evidence

ORD record: ord-a971d45f1a49477b9789a7b015db85d9
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409917B2

Reaction notes

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