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

HRID 891691Notes

Reaction equation

HRID 891691 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.[Si:46]([O:63][CH:64]1[CH2:67][NH:66][CH2:65]1)([C:59]([CH3:62])([CH3:61])[CH3:60])([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.C(P(C#N)(CC)=O)C.C(N(CC)CC)C>CN(C)C=O>[Si:46]([O:63][CH:64]1[CH2:65][N:66]([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]([CH3:43])([CH3:42])[CH3:41])([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:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=4)=[O:20])[CH2:12]3)[S:7][CH:8]=2)=[O:3])[CH2:67]1)([C:59]([CH3:62])([CH3:60])[CH3:61])([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 13586794DiethylphosphorylcyanideHCID 178425313-((Tert-butyldiphenylsilyl)oxy)azetidineHCID 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 131725366p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(3-t-butyldiphenylsilyloxyazetidine-1-carbonyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylateYield 32.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Subsequently, 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 (1.71 g, 2.53 mmol) and 3-t-butyldiphenylsilyloxyazetidine (947 mg, 3.04 mmol) (obtained as described above) in dimethylformamide (86 ml) were added diethylphosphoryl cyanide (461 μl, 3.04 mmol) and triethylamine (426 μl, 3.04 mmol) in an ice bath under an atmosphere of nitrogen. The mixture was stirred at room temperature for 5.5 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 sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using toluene:acetonitrile (4:1) as the eluant to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(3-t-butyldiphenylsilyloxyazetidine-1-carbonyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate (789 mg, yield 32%).

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 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-a1cb9207f03041d69f6da33259820a21
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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