tert-Butanol → Benzyl ((2R,3S)-2-((1-(2-((tert-butoxycarbonyl)amino)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-1-(2,4-dimethoxybenzyl)-4-oxoazetidin-3-yl)(4-methoxybenzyl)carbamate

HRID 708473Notes

Reaction equation

HRID 708473 reaction equation
[CH3:1][O:2][C:3]1[CH:37]=[C:36]([O:38][CH3:39])[CH:35]=[CH:34][C:4]=1[CH2:5][N:6]1[C@H:9]([CH2:10][C:11]#[CH:12])[C@H:8]([N:13]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[C:14](=[O:23])[O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:7]1=[O:33].C(O)(C)(C)C.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].[C:58]([NH:65][CH2:66][CH2:67][N:68]=[N+:69]=[N-:70])([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59]>CS(C)=O.CCOC(C)=O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[C:61]([O:60][C:58]([NH:65][CH2:66][CH2:67][N:68]1[CH:12]=[C:11]([CH2:10][C@@H:9]2[C@H:8]([N:13]([CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[C:14](=[O:23])[O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:7](=[O:33])[N:6]2[CH2:5][C:4]2[CH:34]=[CH:35][C:36]([O:38][CH3:39])=[CH:37][C:3]=2[O:2][CH3:1])[N:70]=[N:69]1)=[O:59])([CH3:64])([CH3:62])[CH3:63]

Participants

9

Reactant 4

HCID 6386tert-ButanolHCID 22323692tert-Butyl (2-azidoethyl)carbamate2×HCID 23667548Sodium Ascorbate2×HCID 118379454Benzyl ((3S,4R)-1-(2,4-dimethoxybenzyl)-2-oxo-4-(prop-2-yn-1-yl)azetidin-3-yl)(4-methoxybenzyl)carbamate

Product 1

HCID 118379592Benzyl ((2R,3S)-2-((1-(2-((tert-butoxycarbonyl)amino)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-1-(2,4-dimethoxybenzyl)-4-oxoazetidin-3-yl)(4-methoxybenzyl)carbamateYield 44.5%

Reagents, catalysts & solvents 4

HCID 24463Copper sulfate pentahydrateCatalyst2×HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of benzyl ((3S,4R)-1-(2,4-dimethoxybenzyl)-2-oxo-4-(prop-2-yn-1-yl)azetidin-3-yl)(4-methoxybenzyl)carbamate (95.6 mg, 0.18 mmol) in a mixture of DMSO (1.2 mL), tert-butanol (1.2 mL) and water (1.2 mL), was added copper(II) sulfate pentahydrate (4.5 mg, 0.018 mmol), sodium L-ascorbate (35.8 mg, 0.18 mmol) and N-Boc-2-azidoethylamine (76 mg, 0.39 mmol). After stirring for 12 h, more copper(II) sulfate pentahydrate (10.6 mg, 0.23 equiv), sodium L-ascorbate (37.4 mg, 1.04 equiv) and N-Boc-2-azidoethylamine (82.1 mg, 2.44 equiv) were added. After stirring for 4 days total, the reaction mixture was diluted with EtOAc and water. The layers were separated, and the aqueous layer was extracted with EtOAc (2×). Combined organic layers were washed with LiCl (5% aq), brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via silica gel chromatography (EtOAc-Hep, 0-40%) to afford the title compound (57.2 mg, 44%). LCMS: Rt=1.06 min, m/z=715.5 (M+1) Method 2m_acidic.

Workup

  1. stirringAfter stirring for 4 days total
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×)
  4. washCombined organic layers were washed with LiCl (5% aq), brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via silica gel chromatography (EtOAc-Hep, 0-40%)

Sources & evidence

ORD record
ord-7a295062c3cf48c4b7cd5cbecb718d3e
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

Loading…