Acetic Acid → p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(3-hydroxyazetidine-1-carbonyl)-1,3-oxazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate

HRID 891539Notes

Reaction equation

HRID 891539 reaction equation
[Si]([O:18][CH:19]1[CH2:22][N:21]([C:23]([C:25]2[N:26]=[C:27]([N:30]3[CH2:33][CH:32]([S:34][C:35]4[C@H:36]([CH3:59])[C@@H:37]5[C@@H:54]([C@H:55]([OH:57])[CH3:56])[C:53](=[O:58])[N:38]5[C:39]=4[C:40]([O:42][CH2:43][C:44]4[CH:49]=[CH:48][C:47]([N+:50]([O-:52])=[O:51])=[CH:46][CH:45]=4)=[O:41])[CH2:31]3)[O:28][CH:29]=2)=[O:24])[CH2:20]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[Na+]>O1CCCC1.C(OCC)(=O)C>[OH:18][CH:19]1[CH2:22][N:21]([C:23]([C:25]2[N:26]=[C:27]([N:30]3[CH2:33][CH:32]([S:34][C:35]4[C@H:36]([CH3:59])[C@@H:37]5[C@@H:54]([C@H:55]([OH:57])[CH3:56])[C:53](=[O:58])[N:38]5[C:39]=4[C:40]([O:42][CH2:43][C:44]4[CH:45]=[CH:46][C:47]([N+:50]([O-:52])=[O:51])=[CH:48][CH:49]=4)=[O:41])[CH2:31]3)[O:28][CH:29]=2)=[O:24])[CH2:20]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5234Sodium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 131725357p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[3-(t-butyldiphenylsilyloxy)-azetidin-1-ylcarbonyl]-1,3-oxazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131725358p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(3-hydroxyazetidine-1-carbonyl)-1,3-oxazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylateYield 38%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

p-Nitrobenzyl (1R,5S,6S)-2-(1-{4-[3-(t-butyldiphenylsilyloxy)-azetidin-1-ylcarbonyl]-1,3-oxazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (1.20 g, 1.43 mmol) (obtained as described in Example 78(1)) in tetrahydrofuran (60 ml) was added to acetic acid (240 μl, 4.30 mmol) and 1 M tetrabutylammonium fluoride in tetrahydrofuran solution (4.30 ml, 4.30 mmol) and the mixture was stirred at room temperature for 4 days. After checking the completion of the reaction, ethyl acetate and saturated aqueous sodium chloride solution 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:methanol(95:5→9:1)) to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(3-hydroxyazetidine-1-carbonyl)-1,3-oxazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (325 mg, yield 38%) 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:methanol(95:5→9:1))

Sources & evidence

ORD record
ord-ca0042e2a67d459f9546bf8195f43a84
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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