Phosphate → (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(3-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylic Acid

HRID 382619Notes

Reaction equation

HRID 382619 reaction equation
[OH:1][C@@H:2]([C@H:4]1[C:33](=[O:34])[N:6]2[C:7]([C:20]([O:22]CC3C=CC([N+]([O-])=O)=CC=3)=[O:21])=[C:8]([C:11]3[S:15][C:14]4=[CH:16][N:17]=[CH:18][N:13]4[C:12]=3[CH3:19])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].P([O-])([O-])([O-])=O.C(NCC1N=CN2C(C3C[C@@H]4[C@@H]([C@H](O)C)C(=O)N4C=3C([O-])=O)=CSC=12)=O.[Na+]>C1COCC1.[Pd]>[OH:1][C@@H:2]([C@H:4]1[C:33](=[O:34])[N:6]2[C:7]([C:20]([OH:22])=[O:21])=[C:8]([C:11]3[S:15][C:14]4=[CH:16][N:17]=[CH:18][N:13]4[C:12]=3[CH3:19])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3]

Participants

6

Reactant 3

HCID 1061PhosphateHCID 120700444-Nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(3-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylateHCID 131722902Sodium (5R,6S)-2-(7-formylaminomethyl imidazo[5,1-b]thiazol-3-yl)-6-((1R)-1-hydroxyethyl)-1-carbapen-2-em-3-carboxylate

Product 1

HCID 12069981(1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(3-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylic AcidYield 56.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 157.3 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(3-methylimidazo[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate in 3 ml of THF and 3 ml of {fraction (1/15)} M phosphate buffer (pH 6.8) was added 0.24 g of 100 Pd-C. The reactor was purged with hydrogen, the reaction mixture was stirred at room temperature for 1 hour. The catalyst was collected by filtration, and washed with 50 ml of water. The filtrate was diluted with 20 ml of ethyl acetate, separated, and the organic layer was further washed with water. The combined aqueous layer was concentrated under reduced pressure to a volume of about 30 ml. The residual concentrate was purified by column chromatography on DIAION HP-20. The fraction containing the aimed product was lyophilized to give 63.5 mg of the title compound.

Workup

  1. customThe reactor was purged with hydrogen
  2. filtrationThe catalyst was collected by filtration
  3. washwashed with 50 ml of water
  4. additionThe filtrate was diluted with 20 ml of ethyl acetate
  5. customseparated
  6. washthe organic layer was further washed with water
  7. concentrationThe combined aqueous layer was concentrated under reduced pressure to a volume of about 30 ml
  8. concentrationThe residual concentrate
  9. customwas purified by column chromatography on DIAION HP-20
  10. additionThe fraction containing the aimed product

Sources & evidence

ORD record
ord-71a5d7e4618e4b8dab7e152463bf2d82
Source dataset
uspto-grants-2001_10
Patent number
US06310056B1

Reaction notes

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