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

HRID 891700Notes

Reaction equation

HRID 891700 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:64]=[CH:63][C:53]([CH2:54][O:55][C:56](=[O:62])[C@H:57]([CH:59]([CH3:61])[CH3:60])[NH2:58])=[CH:52][CH:51]=1)([O-:49])=[O:48].C(P(C#N)(CC)=O)C.C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH3:60][CH:59]([CH3:61])[C@H:57]([NH:58][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])([CH3:38])[CH3:39])[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)=[O:3])[C:56]([O:55][CH2:54][C:53]1[CH:63]=[CH:64][C:50]([N+:47]([O-:49])=[O:48])=[CH:51][CH:52]=1)=[O:62]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 13586794DiethylphosphorylcyanideHCID 69544143L-valine 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 131725368p-nitrobenzyl(1R,5S,6S)-2-{1-[4-((1S)-2-methyl-1-(p-nitrobenzyloxycarbonyl)-propylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylateYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution 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 (1.00 g, 1.48 mmol) (obtained as described in Reference Example 41(7)) and L-valine p-nitrobenzyl ester hydrochloride (514 mg, 1.78 mmol) (obtained as described in Reference Example 46(2)) in dimethylformamide (50 ml) were added diethylphosphoryl cyanide (275 μl, 1.78 mmol) and diisopropylethylamine (620 μl, 3.56 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 10% aqueous sodium chloride solution. The obtained organic layer was washed successively 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 using n-hexane:ethyl acetate (2:1→1:1) as the eluant to afford p-nitrobenzyl(1R,5S,6S)-2-{1-[4-((1S)-2-methyl-1-(p-nitrobenzyloxycarbonyl)-propylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate (1.15 g, yield 86%).

Workup

  1. customthe completion of the reaction
  2. customthe reaction mixture was partitioned between ethyl acetate and 10% aqueous sodium chloride solution
  3. washThe obtained organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous sodium 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-655a9ee33b2a4cea94032a374272f982
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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