Diisopropylethylamine → benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[(5R)-5-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-2-oxo-1,3-oxazolidin-3-yl]methyl]-4-oxoazetidin-3-yl]amino]-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxycyclopropane-1-carboxylate

HRID 708392Notes

Reaction equation

HRID 708392 reaction equation
[CH:1]([O:14][C:15]([C:17]1([O:20]/[N:21]=[C:22](/[C:26]2[N:27]=[C:28]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[S:29][CH:30]=2)\[C:23]([OH:25])=O)[CH2:19][CH2:18]1)=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:72][C@@H:73]1[C:76](=[O:77])[NH:75][C@@H:74]1[CH2:78][N:79]1[CH2:83][C@@H:82]([CH2:84][NH:85][C:86](=[O:92])[O:87][C:88]([CH3:91])([CH3:90])[CH3:89])[O:81][C:80]1=[O:93]>CN(C=O)C.C(Cl)Cl.CN(C=O)C>[C:88]([O:87][C:86]([NH:85][CH2:84][C@H:82]1[O:81][C:80](=[O:93])[N:79]([CH2:78][C@@H:74]2[C@H:73]([NH:72][C:23](=[O:25])/[C:22](=[N:21]\[O:20][C:17]3([C:15]([O:14][CH:1]([C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=4)=[O:16])[CH2:18][CH2:19]3)/[C:26]3[N:27]=[C:28]([NH:31][C:32]([O:34][C:35]([CH3:37])([CH3:38])[CH3:36])=[O:33])[S:29][CH:30]=3)[C:76](=[O:77])[NH:75]2)[CH2:83]1)=[O:92])([CH3:91])([CH3:89])[CH3:90]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118380020(Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acidHCID 131733752tert-butyl (((R)-3-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-2-oxooxazolidin-5-yl)methyl)carbamate

Product 1

HCID 140689357benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[(5R)-5-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-2-oxo-1,3-oxazolidin-3-yl]methyl]-4-oxoazetidin-3-yl]amino]-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxycyclopropane-1-carboxylateYield 72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent2×

Procedure

To a solution of (Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (1.29 g, 2.28 mmol) and HATU (909 mg, 2.39 mmol) in DMF:DCM (3:1, 9.0 mL) at 0° C. was added DIPEA (1.0 mL, 5.72 mmol). After 15 min of stirring at 0° C. tert-butyl (((R)-3-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-2-oxooxazolidin-5-yl)methyl)carbamate (715 mg, 2.28 mmol) was added as a solution in DMF:DCM (1:1, 9 mL) followed by a DMF (1.5 mL) wash. After 1.2 h at rt it was diluted with EtOAc and washed with LiCl (5% aq). The aqueous layer was extracted with EtOAc (3×) and the combined organic layers were washed with LiCl (5% aq), NaHCO3 (aq satd), brine, dried over Na2SO4 and concentrated in vacuo. The crude residue was purified via silica gel chromatography (EtOAc-Heptane, 5-90%) to afford the title compound (1.357 g, 72%) as a white solid. LCMS: Rt=1.04 min, m/z=834.4 (M+1) Method 2m_acidic.

Workup

  1. washwash
  2. additionAfter 1.2 h at rt it was diluted with EtOAc
  3. washwashed with LiCl (5% aq)
  4. extractionThe aqueous layer was extracted with EtOAc (3×)
  5. washthe combined organic layers were washed with LiCl (5% aq), NaHCO3 (aq satd), brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified via silica gel chromatography (EtOAc-Heptane, 5-90%)

Sources & evidence

ORD record
ord-428b16a3e30140818dd5a809f24ff1ad
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

Loading…