Triethylamine → p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(p-nitrobenzyloxycarbonylmethyl)carbamoyl-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate

HRID 891687Notes

Reaction equation

HRID 891687 reaction equation
[C:1]([C:4]1[N:5]=[C:6]([N:9]2[CH2:12][CH:11]([S:13][C:14]3[C@H:15]([CH3:45])[C@@H:16]4[C@@H:33]([C@H:34]([O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[CH3:35])[C:32](=[O:44])[N:17]4[C:18]=3[C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=3)=[O:20])[CH2:10]2)[S:7][CH:8]=1)([OH:3])=O.Cl.[N+:47]([C:50]1[CH:61]=[CH:60][C:53]([CH2:54][O:55][C:56](=[O:59])[CH2:57][NH2:58])=[CH:52][CH:51]=1)([O-:49])=[O:48].C(P(C#N)(CC)=O)C.C(N(CC)CC)C>CN(C)C=O>[N+:47]([C:50]1[CH:51]=[CH:52][C:53]([CH2:54][O:55][C:56]([CH2:57][NH:58][C:1]([C:4]2[N:5]=[C:6]([N:9]3[CH2:10][CH:11]([S:13][C:14]4[C@H:15]([CH3:45])[C@@H:16]5[C@@H:33]([C@H:34]([O:36][Si:37]([C:40]([CH3:41])([CH3:42])[CH3:43])([CH3:38])[CH3:39])[CH3:35])[C:32](=[O:44])[N:17]5[C:18]=4[C:19]([O:21][CH2:22][C:23]4[CH:24]=[CH:25][C:26]([N+:29]([O-:31])=[O:30])=[CH:27][CH:28]=4)=[O:20])[CH2:12]3)[S:7][CH:8]=2)=[O:3])=[O:59])=[CH:60][CH:61]=1)([O-:49])=[O:48]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 13586794DiethylphosphorylcyanideHCID 22401149Glycine p-nitrobenzyl ester hydrochlorideHCID 131725364p-nitrobenzyl (1R,5S,6S)-2-[1-(4-carboxy-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methyl-carbapen-2-em-3-carboxylate

Product 1

HCID 131725326p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(p-nitrobenzyloxycarbonylmethyl)carbamoyl-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Subsequently, to a suspension of p-nitrobenzyl (1R,5S,6S)-2-[1-(4-carboxy-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate (207.4 mg, 0.31 mmol) (obtained as described in Reference Example 41(7)) and glycine p-nitrobenzyl ester hydrochloride (116 mg, 0.47 mmol) (obtained as described above) in dimethylformamide (10.5 ml) were added diethylphosphoryl cyanide (0.072 ml, 0.47 mmol) and triethylamine (0.14 ml, 1.00 mmol) in an ice bath under an atmosphere of nitrogen. The mixture was stirred at room temperature for 2 hours. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The obtained organic layer was washed successively with a 0.5M aqueous hydrochloric acid solution, saturated aqueous sodium hydrogencarbonate solution, and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using toluene:acetonitrile (3:1) as the eluant to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(p-nitrobenzyloxycarbonylmethyl)carbamoyl-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate (209.7 mg, yield 77%) as a pale yellow syrup.

Workup

  1. customthe completion of the reaction
  2. customthe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution
  3. washThe obtained organic layer was washed successively with a 0.5M aqueous hydrochloric acid solution, saturated aqueous sodium hydrogencarbonate solution, and saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-d039c5d13d1144798ec1a62d14ebe341
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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