Methanol → Tert-butyl 3-(1-aminoethyl)-3-pyridin-2-ylazetidine-1-carboxylate

HRID 2100302Notes

Reaction equation

[C:1]([C:3]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)#[N:2].[CH3:20][Mg+].[Br-].CO.[BH4-].[Na+]>C1(C)C=CC=CC=1.C(OCCCC)CCC>[NH2:2][CH:1]([C:3]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)[CH3:20]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of tert-butyl 3-cyano-3-pyridin-2-ylazetidine-1-carboxylate (I-2, 5.0 g, 19.3 mmol) in toluene (100 mL) at room temperature was treated with MeMgBr (55 mL of a 1.0 M solution in dibutyl ether) dropwise over 15 min. After 18 h, the reaction was cooled to 0° C. and treated with MeOH (30 mL) and NaBH4 (1.3 g, 33.2 mmol). After 10 min, the reaction was quenched with the slow addition of saturated aqueous NH4Cl (75 mL), diluted with H2O (75 mL), and extracted with EtOAc (3×150 mL). The combined extracts were dried (Na2SO4) and concentrated under reduced pressure to afford tert-butyl 3-(1-aminoethyl)-3-pyridin-2-ylazetidine-1-carboxylate (I-3). This material was fully resolved into 1R and 1S isomers (>99% ee) using a ChiralPak AD column. NOE analysis of Mosher's amides confirmed the absolute stereochemistry of each isomer. Analytical LCMS: single peak (214 nm), 2.689 min.

Workup

waitAfter 10 min
customthe reaction was quenched with the slow addition of saturated aqueous NH4Cl (75 mL)
additiondiluted with H2O (75 mL)
extractionextracted with EtOAc (3×150 mL)
dry with materialThe combined extracts were dried (Na2SO4)
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-c6cba978967f42228ef4eff181e526b0
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07572792B2

Reaction notes

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