Pyridine → HCID 131714550, compound

HRID 482938Notes

Reaction equation

HRID 482938 reaction equation
[CH2:1]([O:8][C:9](=[O:26])[CH2:10][NH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:14][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:27](Cl)(Cl)=[O:28].N1C=CC=CC=1.[C:37]1([CH2:43][O:44][C:45]([NH:47][C@H:48]2[CH2:51][NH:50][C:49]2=[O:52])=[O:46])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.CN(C1C=CC=CN=1)C.C(N(CC)CC)C>C1(C)C=CC=CC=1>[C:37]1([CH2:43][O:44][C:45]([NH:47][C@H:48]2[CH2:51][N:50]([C:49]([N:11]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)=[CH:14][CH:13]=3)[CH2:10][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:26])=[O:52])[C:27]2=[O:28])=[O:46])[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

8

Reactant 6

HCID 1049PyridineHCID 6371PhosgeneHCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 12834624benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamateHCID 20243557HCID 20243557, compound

Product 1

HCID 131714550HCID 131714550, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

Benzyl-N-(4-benzyloxyphenyl)glycinate (694 mg, 2.0 mmole) was dissolved in 6 ml of dry toluene and cooled to 0° C. A phosgene solution (2.9 ml, 12.5% in toluene) was added to the reaction mixture followed by the dropwise solution of pyridine (0.348 ml, 4.3 mmol) with rapid stirring. The reaction was stirred for 1.5 hours at 0° C. and then allowed to warm to room temperature. The precipitate of pyridinium hydrochloride was filtered under argon, and the volatiles were removed from the filtrate. This was dissolved in 4 ml of dry tetrahydrofuran and cooled to 0° C. To this solution was added (S)-3-[[(phenylmethoxy)carbonyl]amino]-2-azetidinone (440 mg, 2.0 mmole) and 36 mg (0.3 mmole) of dimethylaminopyridine. Triethylamine (0.307 ml, 2.2 mmol) was then added dropwise, and the reaction mixture was allowed to warm to room temperature and stir overnight. The product was extracted with ethyl acetate from dilute aqueous hydrochloric acid. The combined organic extracts were dried with sodium sulfate and the volatiles removed. The residue was purified by flash chromatography on silica (LPS-1) (eluting with 1:1 ethyl acetate/hexane) to yield 465 mg of the title compound.

Workup

  1. temperatureto warm to room temperature
  2. filtrationThe precipitate of pyridinium hydrochloride was filtered under argon
  3. customthe volatiles were removed from the filtrate
  4. dissolutionThis was dissolved in 4 ml of dry tetrahydrofuran
  5. temperaturecooled to 0° C
  6. temperatureto warm to room temperature
  7. stirringstir overnight
  8. extractionThe product was extracted with ethyl acetate from dilute aqueous hydrochloric acid
  9. dry with materialThe combined organic extracts were dried with sodium sulfate
  10. customthe volatiles removed
  11. customThe residue was purified by flash chromatography on silica (LPS-1) (eluting with 1:1 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2024cf6c85024b45af168c89d044c5f7
Source dataset
uspto-grants-1986_03
Patent number
US04576749

Reaction notes

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