Pyridine → (3S-trans)-3-[[(t-Butyloxy)carbonyl]amino]-4-methyl-2-oxo-1-azetidinecarboxylic acid, [(phenylmethoxy)carbonyl]methyl ester

HRID 637913Notes

Reaction equation

HRID 637913 reaction equation
[C:1]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)(=[O:4])[CH2:2][OH:3].[C:13](Cl)(Cl)=[O:14].N1C=CC=CC=1.[C:23]([O:27][C:28]([NH:30][C@H:31]1[C@H:34]([CH3:35])[NH:33][C:32]1=[O:36])=[O:29])([CH3:26])([CH3:25])[CH3:24].ClC([O-])=O.N1CCC1=O>C(N(CC)CC)C>[C:23]([O:27][C:28]([NH:30][C@H:31]1[C@H:34]([CH3:35])[N:33]([C:32]([O:3][CH2:2][C:1]([O:5][CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[O:4])=[O:36])[C:13]1=[O:14])=[O:29])([CH3:25])([CH3:24])[CH3:26]

Participants

8

Reactant 6

HCID 1049PyridineHCID 6371PhosgeneHCID 1367212-AzetidinoneHCID 561337Benzyl 2-hydroxyacetateHCID 13155285tert-Butyl ((2S,3S)-2-methyl-4-oxoazetidin-3-yl)carbamateHCID 21226386Carbonochloridate

Product 1

HCID 57136207(3S-trans)-3-[[(t-Butyloxy)carbonyl]amino]-4-methyl-2-oxo-1-azetidinecarboxylic acid, [(phenylmethoxy)carbonyl]methyl ester

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent2×

Procedure

To 664 mg (4.0 mmol) of benzyl glycolate was added 5.8 ml of 12.5% phosgene (in toluene) at 0° C. To this solution at 0° C. was added pyridine (0.372 ml, 4.6 mmol) dropwise. The reaction was allowed to stir at room temperature for 2 hours and was then filtered under argon. Most of the volatiles were removed under vacuum without external heating, and the residual chloroformate was dissolved in methylene chloride (8 ml). Approximately half of this solution was added to (3S-trans)-3-[[(t-butyloxy)carbonyl]amino]-4-methyl-2-azetidinone (440 mg, 2.0 mmol), and the resulting solution was cooled to -20° C. Triethylamine (0.293 ml, 2.1 mmol) was then added dropwise. After 2 hours at -20° C., the remaining chloroformate was added to the azetidinone reaction mixture followed by 0.293 ml of triethylamine. After 3 hours at -20° C., the product was extracted from aqueous KH2PO4 with three portions of ethyl acetate. The combined organic layers were dried over sodium sulfate, and the volatiles were removed. The residue was subjected to column chromatography on silica gel (eluting with 35% ethyl acetate-hexane) to yield 488 mg of the title compound.

Workup

  1. filtrationwas then filtered under argon
  2. customMost of the volatiles were removed under vacuum without external heating
  3. dissolutionthe residual chloroformate was dissolved in methylene chloride (8 ml)
  4. temperaturethe resulting solution was cooled to -20° C
  5. waitAfter 2 hours at -20° C.
  6. waitAfter 3 hours at -20° C.
  7. extractionthe product was extracted from aqueous KH2PO4 with three portions of ethyl acetate
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. customthe volatiles were removed

Sources & evidence

ORD record
ord-441fd5c60312465d9e2ee1c11b7648d6
Source dataset
uspto-grants-1985_12
Patent number
US04559335

Reaction notes

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