Diphenylphosphinic chloride → (5R,6S)-2-[2-(4-Carbamoyloxypiperidin-1-yl)-2-iminoethylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylic acid

HRID 622427Notes

Reaction equation

HRID 622427 reaction equation
C(N(C(C)C)CC)(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[OH:25][C@@H:26]([C@H:28]1[C:48](=[O:49])[N:30]2[CH:31]([C:35]([O:37]CC3C=CC([N+]([O-])=O)=CC=3)=[O:36])[C:32](=O)[CH2:33][C@H:29]12)[CH3:27].Cl.[C:51]([O:54][CH:55]1[CH2:60][CH2:59][N:58]([C:61](=[NH:64])[CH2:62][SH:63])[CH2:57][CH2:56]1)(=[O:53])[NH2:52]>C(#N)C.O1CCCC1.P([O-])([O-])([O-])=O.[C].[Pd]>[C:51]([O:54][CH:55]1[CH2:60][CH2:59][N:58]([C:61](=[NH:64])[CH2:62][S:63][C:32]2[CH2:33][C@@H:29]3[C@@H:28]([C@H:26]([OH:25])[CH3:27])[C:48](=[O:49])[N:30]3[C:31]=2[C:35]([OH:37])=[O:36])[CH2:57][CH2:56]1)(=[O:53])[NH2:52]

Participants

9

Reactant 4

HCID 73910Diphenylphosphinic chlorideHCID 81531Diisopropylethylamine2×HCID 11198839(4-Nitrophenyl)methyl (5R,6S)-6-((1R)-1-hydroxyethyl)-3,7-dioxo-1-azabicyclo(3.2.0)heptane-2-carboxylateHCID 212929412-(4-Carbamoyloxypiperidin-1-yl)-2-iminoethylmercaptan hydrochloride

Product 1

HCID 22839818(5R,6S)-2-[2-(4-Carbamoyloxypiperidin-1-yl)-2-iminoethylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylic acidYield 19%

Reagents, catalysts & solvents 4

HCID 178418390HCID 178418390, compoundCatalystHCID 1061PhosphateSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

1.83 ml of diisopropylethylamine and 2.18 ml of diphenylphosphoryl chloride were added dropwise to an ice-cooled solution of 3.48 g of 4-nitrobenzyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylate in 20 ml of anhydrous acetonitrile, and the mixture was stirred for one hour with ice-cooling. The reaction mixture was then added to a mixture of 2.1 ml of diisopropylethylamine in 70 ml of tetrahydrofuran and 60 ml of 0.1M phosphate buffer solution (pH 7.0), which had been cooled with ice and salt, together with 10 ml of an aqueous solution of 3.17 g of 2-(4-carbamoyloxypiperidin-1-yl)-2-iminoethylmercaptan hydrochloride, and the resulting mixture was stirred for 5 minutes. The reaction mixture was then subjected to hydrogenation at room temperature for 2 hours, in the presence of 3.0 g of 10% palladium-carbon. The hydrogenated reaction mixture was worked up in the same manner as in Example 1(3), giving 783 mg of the title compound.

Workup

  1. temperaturecooling
  2. stirringthe resulting mixture was stirred for 5 minutes

Sources & evidence

ORD record
ord-b8bc481851a240898d8564c3274404a1
Source dataset
uspto-grants-1988_09
Patent number
US04771046

Reaction notes

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