Benzyl chloroformate → Benzyl((2S,3S)-1-(2,4-dimethoxybenzyl)-2-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-oxoazetidin-3-yl)carbamate

Reaction equation

[NH2:1][C@H:2]1[C@@H:5]([C@@H:6]2[CH2:10][O:9][C:8]([CH3:12])([CH3:11])[O:7]2)[N:4]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=2[O:22][CH3:23])[C:3]1=[O:24].C([O-])(O)=O.[Na+].Cl[C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32]>>[CH3:23][O:22][C:15]1[CH:16]=[C:17]([O:20][CH3:21])[CH:18]=[CH:19][C:14]=1[CH2:13][N:4]1[C:3](=[O:24])[C@@H:2]([NH:1][C:31](=[O:32])[O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C@H:5]1[C@@H:6]1[CH2:10][O:9][C:8]([CH3:12])([CH3:11])[O:7]1

Participants

Reactant 3

HCID 10387Benzyl chloroformate

HCID 516892Sodium Bicarbonate

HCID 13826540(3S,4S)-3-amino-1-(2,4-dimethoxybenzyl)-4-[(R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-azetidinone

Product 1

HCID 13535989Benzyl((2S,3S)-1-(2,4-dimethoxybenzyl)-2-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-oxoazetidin-3-yl)carbamateYield 45%

Procedure

To the crude organic solution from step 3 (EtOAc, 4 L) cooled to 0° C. was added saturated NaHCO3 (aq, 2.05 L) followed by benzyl chloroformate (205 mL, 1.43 mol), drop-wise over 1 h. After stirring at rt for 2 h the layers were separated and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with water, brine, dried over Na2SO4 and concentrated in vacuo. The crude residue was treated with MeOH (2 L), filtered and washed with MeOH (2×200 mL) to afford pure title compound (155 g) as a white solid. The mother liquor was cooled to −20° C. for 12 h and the resulting precipitate was collected by filtration, affording additional title compound (90 g) for a combined 45% yield over 4 steps. LCMS: m/z=471.1 (M+1).