Acetic Acid → HCID 131725304, compound

HRID 891487Notes

Reaction equation

HRID 891487 reaction equation
[Si]([O:8][CH2:9][C:10]1[N:11]=[C:12]([N:15]2[CH2:18][CH:17]([S:19][C:20]3[C@H:21]([CH3:44])[C@@H:22]4[C@@H:39]([C@H:40]([OH:42])[CH3:41])[C:38](=[O:43])[N:23]4[C:24]=3[C:25]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][CH:30]=3)=[O:26])[CH2:16]2)[S:13][CH:14]=1)(C(C)(C)C)(C)C.C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[OH:8][CH2:9][C:10]1[N:11]=[C:12]([N:15]2[CH2:16][CH:17]([S:19][C:20]3[C@H:21]([CH3:44])[C@@H:22]4[C@@H:39]([C@H:40]([OH:42])[CH3:41])[C:38](=[O:43])[N:23]4[C:24]=3[C:25]([O:27][CH2:28][C:29]3[CH:30]=[CH:31][C:32]([N+:35]([O-:37])=[O:36])=[CH:33][CH:34]=3)=[O:26])[CH2:18]2)[S:13][CH:14]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 2724141Tetrabutylammonium FluorideHCID 131725303HCID 131725303, compound

Product 1

HCID 131725304HCID 131725304, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of p-nitrobenzyl (1R,5S,6S)-2-[1-(4-t-butyldimethylsilyloxymethyl-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (719 mg, 1.09 mmol) (obtained as described in Example 20(1)) in anhydrous tetrahydrofuran (36 ml) were added sequentially acetic acid (0.19 ml, 3.3 mmol) and a solution of tetra-n-butylammonium fluoride in tetrahydrofuran (3.3 ml, 3.3 mmol) in an ice bath. The resulting mixture was stirred at room temperature overnight. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate and the aqueous layer was further extracted with ethyl acetate. The organic layers were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using ethyl acetate: methanol (15:1) as the eluant to afford the desired compound p-nitrobenzyl (1R,5S,6S)-2-[1-(4-hydroxymethyl-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (426.2 mg, yield 72%) as a yellow syrup.

Workup

  1. customthe completion of the reaction
  2. customthe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate
  3. extractionthe aqueous layer was further extracted with ethyl acetate
  4. washThe organic layers were washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-b2215348281142fcbbdec47d6378b3a4
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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