Acetic Acid → HCID 131725324, compound

HRID 891507Notes

Reaction equation

HRID 891507 reaction equation
[Si]([O:8][CH2:9][C@@H:10]([NH:15][C:16]([C:18]1[N:19]=[C:20]([N:23]2[CH2:26][CH:25]([S:27][C:28]3[C@H:29]([CH3:52])[C@@H:30]4[C@@H:47]([C@H:48]([OH:50])[CH3:49])[C:46](=[O:51])[N:31]4[C:32]=3[C:33]([O:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[CH:39][CH:38]=3)=[O:34])[CH2:24]2)[S:21][CH:22]=1)=[O:17])[C@@H:11]([CH3:14])[CH2:12][CH3:13])(C(C)(C)C)(C)C.C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>O1CCCC1.O>[OH:8][CH2:9][C@@H:10]([NH:15][C:16]([C:18]1[N:19]=[C:20]([N:23]2[CH2:24][CH:25]([S:27][C:28]3[C@H:29]([CH3:52])[C@@H:30]4[C@@H:47]([C@H:48]([OH:50])[CH3:49])[C:46](=[O:51])[N:31]4[C:32]=3[C:33]([O:35][CH2:36][C:37]3[CH:38]=[CH:39][C:40]([N+:43]([O-:45])=[O:44])=[CH:41][CH:42]=3)=[O:34])[CH2:26]2)[S:21][CH:22]=1)=[O:17])[C@@H:11]([CH3:14])[CH2:12][CH3:13]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 131725323HCID 131725323, compound

Product 1

HCID 131725324HCID 131725324, compoundYield 60.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

p-Nitrobenzyl (1R,5S,6S)-2-(1-{4-[(1S,2S)-1-(t-butyldimethylsilyloxymethyl)-2-methyl-butylcarbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (760 mg, 0.982 mmol) (obtained as described in Example 43(1)) in tetrahydrofuran (38ml) was added to acetic acid (169 μl, 2.95 mmol) and 1 M tetrabutylammonium fluoride in tetrahydrofuran solution (2.95 ml, 2.95 mmol) and the mixture was stirred at room temperature for 3 days. After checking the completion of the reaction, ethyl acetate and water were added to the reaction mixture. The resulting mixture was shaken in a separatory funnel and the ethyl acetate layer was separated, washed with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column (eluant: ethyl acetate→ethyl acetate: methanol (9:1)) to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-((1S,2S)-1-hydroxymethyl-2-methylbutylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (390 mg, yield 60%) as a pale yellow solid.

Workup

  1. additionwere added to the reaction mixture
  2. stirringThe resulting mixture was shaken in a separatory funnel
  3. customthe ethyl acetate layer was separated
  4. washwashed with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography on a silica gel column (eluant: ethyl acetate→ethyl acetate: methanol (9:1))

Sources & evidence

ORD record
ord-96aa213407784fce9c51404c39e8a979
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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