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

HRID 708320Notes

Reaction equation

HRID 708320 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

4

Reactant 3

HCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 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).

Workup

  1. customwere separated
  2. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. additionThe crude residue was treated with MeOH (2 L)
  7. filtrationfiltered
  8. washwashed with MeOH (2×200 mL)

Sources & evidence

ORD record
ord-dac6329e107b46bc823cdfffb0b2059f
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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