Diisopropylethylamine → HCID 67674080, compound

HRID 1585510Notes

Reaction equation

HRID 1585510 reaction equation
[C:1]([O:5][C:6](=[O:10])[C:7](Cl)=[O:8])([CH3:4])([CH3:3])[CH3:2].[Cl-].[Ca+2].[Cl-].[C:14]([O:18][C:19](=[O:39])[NH:20][C@@H:21]1[C:24](=[O:25])[NH:23][C@@H:22]1[CH2:26][CH2:27][C:28](=[O:38])[CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])([CH3:17])([CH3:16])[CH3:15].C(N(CC)C(C)C)(C)C>C(Cl)Cl>[C:1]([O:5][C:6](=[O:10])[C:7]([N:23]1[C:24](=[O:25])[C@@H:21]([NH:20][C:19]([O:18][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:39])[C@H:22]1[CH2:26][CH2:27][C:28](=[O:38])[CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5284359Calcium ChlorideHCID 11126621tert-Butyl 2-chloro-2-oxoacetateHCID 67674094HCID 67674094, compound

Product 1

HCID 67674080HCID 67674080, compoundYield 72.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

To a solution of 490.7 g (3.0 Mol) chloro-oxo-acetic acid tert-butyl ester (6) in 4.41 l methylene chloride was added 577 g (5.7 Mol) calcium chloride. The suspension was cooled to 0-5° C. A cold (0° C.) solution of 575 g (1.48 Mol) (2R, 3S)-[2-[4-(tert-butyl-dimethyl-silanyloxy)-3-oxo-butyl]-4-oxo-azetidin-3-yl]-carbamic acid tert-butyl ester (5) and 385 g (3.0 Mol) N,N-diisopropylethylamine was added at such a rate that the temperature does not rise above 5° C. (1.5 h). The reaction mixture was warmed to 23° C. and stirred for 1 h. The solids were removed by filtration and washed with 1.0 l methylene chloride. The combined filtrates were extracted with 1.5 l water, twice with 1.5 l sodium bicarbonate 5% and once again with 1.5 l water. The aqueous phases were extracted with 1.0 l methylene chloride. The combined organic phases were dried over 500 g sodium sulfate and filtered. The solids were washed with 1 l methylene chloride. The combined filtrates were concentrated to a volume of 5.0 l. To this solution 20 l n-hexane was added and the mixture was concentrated to a volume of 10 l. The product was allowed to crystallize while stirring at room temperature for 16 h. The precipitate was collected by filtration, washed with 4 l n-hexane and dried at 0.1 torr at 40° C. to yield 550 g of (2R, 3S)-{3-tert-butoxy carbonylamino-2-[4-(tert-butyl-dimethyl-silanyloxy)-3-oxo-butyl]-4-oxo-azetidin-1-yl}-oxo-acetic acid tert-butyl ester (7) as colorless crystals (69% Th.); m.p.: 102-103° C.

Workup

  1. customdoes not rise above 5° C.
  2. custom(1.5 h)
  3. temperatureThe reaction mixture was warmed to 23° C.
  4. customThe solids were removed by filtration
  5. washwashed with 1.0 l methylene chloride
  6. extractionThe combined filtrates were extracted with 1.5 l water, twice with 1.5 l sodium bicarbonate 5% and once again with 1.5 l water
  7. extractionThe aqueous phases were extracted with 1.0 l methylene chloride
  8. dry with materialThe combined organic phases were dried over 500 g sodium sulfate
  9. filtrationfiltered
  10. washThe solids were washed with 1 l methylene chloride
  11. concentrationThe combined filtrates were concentrated to a volume of 5.0 l
  12. additionTo this solution 20 l n-hexane was added
  13. concentrationthe mixture was concentrated to a volume of 10 l
  14. customto crystallize
  15. stirringwhile stirring at room temperature for 16 h
  16. filtrationThe precipitate was collected by filtration
  17. washwashed with 4 l n-hexane
  18. customdried at 0.1 torr at 40° C.

Sources & evidence

ORD record
ord-150d3293558f46088e6267b09cd493a9
Source dataset
uspto-grants-1999_08
Patent number
US05939410

Reaction notes

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