Dimethylformamide → p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[N-methyl-N-(p-nitrobenzyloxycarbonyl)methyl-carbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylate

HRID 891694Notes

Reaction equation

HRID 891694 reaction equation
C([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)(O)=O.Cl.[N+:47]([C:50]1[CH:62]=[CH:61][C:53]([CH2:54][O:55][C:56](=[O:60])[CH2:57][NH:58][CH3:59])=[CH:52][CH:51]=1)([O-:49])=[O:48].C(P(C#N)(CC)=O)C.C(N(CC)CC)C.CN(C)[CH:80]=[O:81]>>[CH3:59][N:58]([CH2:57][C:56]([O:55][CH2:54][C:53]1[CH:52]=[CH:51][C:50]([N+:47]([O-:49])=[O:48])=[CH:62][CH:61]=1)=[O:60])[C:80]([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]([CH3:41])([CH3:43])[CH3:42])([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:24]=[CH:25][C:26]([N+:29]([O-:31])=[O:30])=[CH:27][CH:28]=3)=[O:20])[CH2:10]2)[S:7][CH:8]=1)=[O:81]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 13586794DiethylphosphorylcyanideHCID 69544074Sarcosine 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 131725367p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[N-methyl-N-(p-nitrobenzyloxycarbonyl)methyl-carbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylateYield 76%

Procedure

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 (1.00 g, 1.51 mmol) (obtained as described in Reference Example 41(7)) and sarcosine p-nitrobenzyl ester hydrochloride (590 mg, 2.26 mmol) (obtained as described in Reference Example 43(2)) in dimethylformamide (30 ml) were added diethylphosphoryl cyanide (0.37 ml, 2.26 mmol) and triethylamine (0.95 ml, 6.80 mmol) in an ice bath under an atmosphere of nitrogen. The mixture was stirred at room temperature for 3 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 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 hexane:ethyl acetate (1:1)→ethyl acetate as the eluant to afford p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[N-methyl-N-(p-nitrobenzyloxycarbonyl)methyl-carbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylate (997 mg, yield 76%).

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 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-9c4377be0b8e482aaeb124c7fb2359ea
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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