Triphenylphosphine → p-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

HRID 891685Notes

Reaction equation

HRID 891685 reaction equation
C([O:4][C:5]([C:7]1[N:8]=[C:9]([N:12]2[CH2:15][CH:14]([S:16][C:17]3[C@H:18]([CH3:48])[C@@H:19]4[C@@H:36]([C@H:37]([O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41])[CH3:38])[C:35](=[O:47])[N:20]4[C:21]=3[C:22]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=3)=[O:23])[CH2:13]2)[S:10][CH:11]=1)=[O:6])C=C.CC1(C)CC(=O)CC(=O)C1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:5]([C:7]1[N:8]=[C:9]([N:12]2[CH2:13][CH:14]([S:16][C:17]3[C@H:18]([CH3:48])[C@@H:19]4[C@@H:36]([C@H:37]([O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:41])[CH3:42])[CH3:38])[C:35](=[O:47])[N:20]4[C:21]=3[C:22]([O:24][CH2:25][C:26]3[CH:27]=[CH:28][C:29]([N+:32]([O-:34])=[O:33])=[CH:30][CH:31]=3)=[O:23])[CH2:15]2)[S:10][CH:11]=1)([OH:6])=[O:4]

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 31358DimedoneHCID 131725365p-nitrobenzyl (1R,5S,6S)-2-[1-(4-allyloxycarbonyl-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 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-carboxylateYield 54.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of p-nitrobenzyl (1R,5S,6S)-2-[1-(4-allyloxycarbonyl-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate (3.73 g, 5.2 mmol) (obtained Reference Example 41(6)) in methylene chloride (180 ml) were added dimedone (1.46 g, 10.4 mmol), tetrakis(triphenylphosphine)palladium(0) (603 mg, 0.522 mmol) and triphenylphosphine (205 mg, 0.783 mmol), and the mixture was stirred at room temperature under an atmosphere of nitrogen for 2 hours. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium chloride solution. The obtained organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using ethyl acetate:methanol (10:1)→methylene chloride:methanol (10:1) as the eluant to afford p-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 (1.91 g, yield 54%) as a pale brown solid.

Workup

  1. customthe completion of the reaction
  2. customthe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium chloride solution
  3. dry with materialThe obtained organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-c5ced4b159994383b4b9a16f72bcaa7a
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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