Diisopropylethylamine → HCID 15381474, compound

HRID 1419466Notes

Reaction equation

HRID 1419466 reaction equation
[SH:1][CH:2]1[CH2:5][N:4]([C:6]2[S:7][CH2:8][CH2:9][N:10]=2)[CH2:3]1.C1(P(O[C:26]2[C@H:27]([CH3:50])[C@@H:28]3[C@@H:45]([C@H:46]([OH:48])[CH3:47])[C:44](=[O:49])[N:29]3[C:30]=2[C:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=2)=[O:32])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C.C(SC1CN(C2SCCN=2)C1)(=O)C>C(#N)C.C(Cl)(Cl)Cl.C(OCC)(=O)C>[S:7]1[CH2:8][CH2:9][N:10]=[C:6]1[N:4]1[CH2:5][CH:2]([S:1][C:26]2[C@H:27]([CH3:50])[C@@H:28]3[C@@H:45]([C@H:46]([OH:48])[CH3:47])[C:44](=[O:49])[N:29]3[C:30]=2[C:31]([O:33][CH2:34][C:35]2[CH:36]=[CH:37][C:38]([N+:41]([O-:43])=[O:42])=[CH:39][CH:40]=2)=[O:32])[CH2:3]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 98153651-(4,5-Dihydro-1,3-thiazol-2-yl)azetidine-3-thiolHCID 11790619S-[1-(4,5-Dihydro-2-thiazolyl)-3-azetidinyl] ethanethioateHCID 15871605p-nitrobenzyl (1R,5R,6S)-2-(di-phenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate2×

Product 1

HCID 15381474HCID 15381474, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 22555007Acetonitrile chloroformSolvent

Procedure

770 mg of 28% sodium methoxide-methanol solution was added to a mixture solution of 862 mg of Compound (18) obtained in the step (b) in 20 ml of anhydrous methanol under ice-cooling and nitrogen gas atmosphere. Then the reaction mixture was stirred for 10 minutes under the same conditions. After reaction, 4 ml of 2N--HCl was added to the reaction mixture and the solvent was removed under reduced pressure to give crude 3-mercapto-1-(thiazolin-2-yl)azetidine [Compound (19)]. Then the crude Compound (19) was dissolved in 15 ml of a mixture solution of anhydrous acetonitrile-chloroform and to this solution were added 2430 mg of p-nitrobenzyl (1R,5R,6S)-2-(di-phenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate [Compound (20)] and 2.8 ml of diisopropylethylamine under ice-cooling and nitrogen gas atmosphere. After stirring the reaction mixture for 2 hours under the same conditions, ethyl acetate was added and the separated organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated saline solution. The solvent was removed and the resulting residue was purified by silica gel column chromatography (chloroform: acetone =1:2) to give 1339 mg [65% yield from Compound (18)] of p-nitrobenzyl (1R,5S,6S)-2-[(1-(thiazolin-2-yl)azetidin-3-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate [Compound (21)].

Workup

  1. temperaturecooling
  2. additionwas added
  3. washthe separated organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated saline solution
  4. customThe solvent was removed
  5. customthe resulting residue was purified by silica gel column chromatography (chloroform: acetone =1:2)

Sources & evidence

ORD record
ord-e33bfb5ec9944aa7bba661bdb18216ed
Source dataset
uspto-grants-1999_03
Patent number
US05886172

Reaction notes

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