Sodium hydride → benzyl ((3S,4R)-1-(2,4-dimethoxybenzyl)-2-oxo-4-(2-oxoethyl)azetidin-3-yl)(4-methoxybenzyl)carbamate

HRID 708471Notes

Reaction equation

HRID 708471 reaction equation
[CH3:1][O:2][C:3]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:4]=1[CH2:5][N:6]1[C:9](=[O:10])[C@@H:8]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:7]1/[CH:22]=[CH:23]/[O:24]C.[H-].[Na+].[CH3:34][O:35][C:36]1[CH:43]=[CH:42][C:39]([CH2:40]Cl)=[CH:38][CH:37]=1>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:4]=1[CH2:5][N:6]1[C@H:7]([CH2:22][CH:23]=[O:24])[C@H:8]([N:11]([CH2:40][C:39]2[CH:42]=[CH:43][C:36]([O:35][CH3:34])=[CH:37][CH:38]=2)[C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]1=[O:10]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 131733783Benzyl ((2R,3S)-1-(2,4-dimethoxybenzyl)-2-((E)-2-methoxyvinyl)-4-oxoazetidin-3-yl)carbamate

Product 1

HCID 118379348benzyl ((3S,4R)-1-(2,4-dimethoxybenzyl)-2-oxo-4-(2-oxoethyl)azetidin-3-yl)(4-methoxybenzyl)carbamateYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of benzyl ((2R,3S)-1-(2,4-dimethoxybenzyl)-2-((E)-2-methoxyvinyl)-4-oxoazetidin-3-yl)carbamate (example 82, step 1, 1.44 g, 3.38 mmol) in DMF (33.8 ml) at −10° C. (salt-ice bath) was addeds sodium hydride (60%, 162 mg, 4.05 mmol). After stirring for 30 min, p-methoxybenzylchloride (506, μL, 3.71 mmol) was added. After warming to 0° C. and stirring for an additional 30 min, it was quenched with NH4Cl (aq, satd) then diluted with EtOAc and LiCl (5% aq). The layers were separated and aqueous layer was extracted with EtOAc (2×). The combined organic layers washed with LiCl (5% aq), brine, dried over Na2SO4 and concd in vacuo. The crude material was subjected to conditions described in example 82, step 2 then purified via silica gel chromatography (EtOAc-Hept, 0-70%) to afford the title compound (684 mg, 38%). LCMS: Rt=0.97 min, m/z=533.2 (M+1) Method 2m_acidic.

Workup

  1. customat −10° C.
  2. stirringstirring for an additional 30 min
  3. customit was quenched with NH4Cl (aq, satd)
  4. additionthen diluted with EtOAc and LiCl (5% aq)
  5. customThe layers were separated
  6. extractionaqueous layer was extracted with EtOAc (2×)
  7. washThe combined organic layers washed with LiCl (5% aq), brine
  8. dry with materialdried over Na2SO4 and concd in vacuo
  9. customthen purified via silica gel chromatography (EtOAc-Hept, 0-70%)

Sources & evidence

ORD record
ord-5cbd38c67c024a538063ccb2afd878aa
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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