Oxalyl chloride → (2R,3R)-N,N-bis-(tert-butoxycarbonylmethyl)-2,3-epoxybutyramide

HRID 1034462Notes

Reaction equation

HRID 1034462 reaction equation
C(Cl)(=O)C(Cl)=O.CCCCC(F)(F)C(O)CC[C@@H]1[C@@H:20](CCCCCCC(O)=O)[C:18](=[O:19])[CH2:17][C@H:16]1[OH:30].C1CCC(NC2CCCCC2)CC1.[NH:47]([CH2:56][C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50]>C(Cl)Cl.CN1CCOCC1>[C:60]([O:59][C:57]([CH2:56][N:47]([CH2:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[C:16](=[O:30])[C@@H:17]1[O:19][C@@H:18]1[CH3:20])=[O:58])([CH3:62])([CH3:63])[CH3:61]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 4393691DI-T-Butyl iminodiacetateHCID 7174909515-Hydroxy Lubiprostone Dicyclohexylammonium Salt

Product 1

HCID 54040080(2R,3R)-N,N-bis-(tert-butoxycarbonylmethyl)-2,3-epoxybutyramide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent4×HCID 79724-MethylmorpholineSolvent

Procedure

A solution of 11.6 g of oxalyl chloride in 25 ml of methylene chloride is added dropwise, in the course of 15 minutes, to a mixture, cooled to -25°, of 20 g of dimethylforinaniide and 115 ml of methylene chloride. The white suspension is stirred for a further 20 minutes at -25°, and a solution of 28.5 g of the dicyclohexylammonium salt of (2R,3R,)-2,3-epoxybutyric acid in 115 ml of methylene chloride is then added in the course of 10 minutes. The reaction mixture is stirred for a further 20 minutes at the same temperature, and a solution of 17.87 g of di-tert-butyl iminodiacetate in 90 ml of methylene chloride and 9.22 ml of N-methylmorpholine are then added dropwise simultaneously in the course of 15 minutes. The cooling bath is removed and the reaction mixture is stirred for 3 hours at room temperature. The white suspension is then filtered through a sintered glass suction filer, the residue is washed with methylene chloride, and the filtrate is diluted with methylene chloride and washed successively with water, 5% aqueous citric acid, saturated aqueous sodium bicarbonate solution and water. The aqueous phases are subsequently extracted twice with methylene chloride, and the combined organic phases are dried and evaporated under a water pump vacuum. The yellow-brown crude product is purified by flash chromatography over silica gel (Merck 9385) using a 9:1 mixture of methylene chloride and ethyl acetate as the mobile phase. (2R,3R)-N,N-Bis-(tert-butoxy-carbonylmethyl)-2,3-epoxybutyramide is obtained in the form of a pale yellow oil, [α]D =+52° (c=1.250% in chloroform).

Workup

  1. stirringThe reaction mixture is stirred for a further 20 minutes at the same temperature
  2. customThe cooling bath is removed
  3. stirringthe reaction mixture is stirred for 3 hours at room temperature
  4. filtrationThe white suspension is then filtered through a sintered glass suction filer
  5. washthe residue is washed with methylene chloride
  6. additionthe filtrate is diluted with methylene chloride
  7. washwashed successively with water, 5% aqueous citric acid, saturated aqueous sodium bicarbonate solution and water
  8. extractionThe aqueous phases are subsequently extracted twice with methylene chloride
  9. customthe combined organic phases are dried
  10. customevaporated under a water pump vacuum
  11. customThe yellow-brown crude product is purified by flash chromatography over silica gel (Merck 9385)
  12. additiona 9:1 mixture of methylene chloride and ethyl acetate as the mobile phase

Sources & evidence

ORD record
ord-76d50f2d7a4c4fd6b0b7a98b54643f2b
Source dataset
uspto-grants-1994_05
Patent number
US05317100

Reaction notes

Loading…