Dicyclohexylcarbodiimide → tert-butyl 2-methyl-2-[(Z)-[2-oxo-2-[[(3S)-2-oxoazetidin-3-yl]amino]-1-[2-(tritylamino)-1,3-thiazol-4-yl]ethylidene]amino]oxypropanoate

HRID 1762393Notes

Reaction equation

HRID 1762393 reaction equation
C1(CO[C:9](=[O:16])[NH:10][C@H:11]2[CH2:14][NH:13][C:12]2=[O:15])C=CC=CC=1.[CH3:17][C:18]([CH3:57])([O:20][C:21](=[O:56])[C:22]([CH3:55])([CH3:54])[O:23]/[N:24]=[C:25](/[C:29]1[N:30]=[C:31]([NH:34][C:35]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[S:32][CH:33]=1)\C(O)=O)[CH3:19].C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1.C([O-])(O)=O.[Na+]>[Pd].O.CN(C=O)C.CO>[CH3:19][C:18]([CH3:57])([O:20][C:21](=[O:56])[C:22]([CH3:55])([CH3:54])[O:23]/[N:24]=[C:25](/[C:29]1[N:30]=[C:31]([NH:34][C:35]([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[S:32][CH:33]=1)\[C:9]([NH:10][C@H:11]1[CH2:14][NH:13][C:12]1=[O:15])=[O:16])[CH3:17]

Participants

10

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 11039088(Z)-alpha-((2-(tert-Butoxy)-1,1-dimethyl-2-oxoethoxy)imino)-2-(tritylamino)thiazol-4-acetic acidHCID 12834624benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamate

Product 1

HCID 88606817tert-butyl 2-methyl-2-[(Z)-[2-oxo-2-[[(3S)-2-oxoazetidin-3-yl]amino]-1-[2-(tritylamino)-1,3-thiazol-4-yl]ethylidene]amino]oxypropanoateYield 59,396.898%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2.20 g (0.01 mmol) of (S)-(2-oxo-3-azetidinyl) carbamic acid phenylmethyl ester, 125 mL of methanol, and 0.68 g of 10% palladium on carbon catalyst was hydrogenated (5 minutes) on a parr apparatus at an initial gauge pressure of 50 psi. After filtration of the catalyst, the solution was concentrated to dryness under reduced pressure. The residual (S)-3-amino-2-azetidinone was dissolved in 10 mL of DMF and added to a mixture of 5.71 g (0.01 mol) of (Z)-α-[[2-(1,1-dimethylethoxy)-1,1-dimethyl-2-oxoethoxy]imino]-2-[(triphenylmethyl)amino]-4-thiazole acetic acid, 40 mL of DMF, 2.06 g (0.01 mol) of N,N'-dicyclohexylcarbodiimide and 1.35 g (0.01 mol) of 1-hydroxybenzotriazole. The mixture was stirred for 4 hours, diluted with 500 mL of water, and adjusted to pH 7.5 with aqueous NaHCO3. The mixture was extracted with four 300 mL portions of ethyl acetate. The combined extracts were washed with water and brine, dried (Na2SO4), decolorized with charcoal, and concentrated to dryness. After purification by HPLC on a Waters Prep 500, using 4:1 ethyl acetate-hexane, 3.8 g of (S,Z)-α-[[2-(1,1-dimethylethoxy)-1,1-dimethyl-2-oxoethoxy]imino]-N-(2-oxo-3-azetidinyl)-2-[(triphenylmethyl)amino]-4-thiazoleacetamide was obtained.

Workup

  1. custom(5 minutes)
  2. filtrationAfter filtration of the catalyst
  3. concentrationthe solution was concentrated to dryness under reduced pressure
  4. dissolutionThe residual (S)-3-amino-2-azetidinone was dissolved in 10 mL of DMF
  5. extractionThe mixture was extracted with four 300 mL portions of ethyl acetate
  6. washThe combined extracts were washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated to dryness
  9. customAfter purification by HPLC on a Waters Prep 500

Sources & evidence

ORD record
ord-a6f7156fe46544b98d978c9b8a031cc5
Source dataset
uspto-grants-1989_05
Patent number
US04831130

Reaction notes

Loading…