Dimethyl Sulfoxide → tert-butyl (2R,5S)-5-formyl-2-[2-(2-{[N-(methoxycarbonyl)-b-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

HRID 629711Notes

Reaction equation

HRID 629711 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH2:12][C@H:13]1[N:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][C@@H:16]([CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[NH:34][C:35](=[O:55])[C@H:36]([CH:42]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[NH:37][C:38]([O:40][CH3:41])=[O:39])[O:15][CH2:14]1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>C(Cl)Cl.O>[CH:12]([C@H:13]1[N:18]([C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[CH2:17][C@@H:16]([CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[NH:34][C:35](=[O:55])[C@H:36]([CH:42]([C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=2)[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[NH:37][C:38]([O:40][CH3:41])=[O:39])[O:15][CH2:14]1)=[O:11]

Participants

8

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 86726307(2R,5R)-5-hydroxymethyl-2-{2-[2-((S)-2-methoxycarbonylamino-3,3-diphenyl-propionylamino)-phenyl]-ethyl}-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 86726317tert-butyl (2R,5S)-5-formyl-2-[2-(2-{[N-(methoxycarbonyl)-b-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of oxalyl chloride (5 eq) in DCM (0.3 M) at −78° C. was added a solution of DMSO (10 eq) in DCM (0.5M). The reaction mixture was stirred at −78° C. for 30 min. A solution of tert-butyl (2R,5R)-5-(hydroxymethyl)-2-[2-(2-{[N-(methoxycarbonyl)-β-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate (Example 185, step 10) (1 eq) in CH2Cl2 (0.2M) was added dropwise and stirred at −40° C. for 1.5 hours. It was then cooled to −78° C. and triethylamine (10 eq)) was added and the reaction mixture was stirred at 0° C. for 1 h. Water was added and the reaction mixture was warmed to rt for 30 min. The mixture was poured into aqueous sodium hydrogen carbonate and the aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with brine, dried with MgSO4 and concentrated under vacuum to afford the title compound as a yellow gum. The material was used in the subsequent step without further purification.

Workup

  1. stirringstirred at −40° C. for 1.5 hours
  2. temperatureIt was then cooled to −78° C.
  3. stirringthe reaction mixture was stirred at 0° C. for 1 h
  4. temperaturethe reaction mixture was warmed to rt for 30 min
  5. extractionthe aqueous layer was extracted with CH2Cl2
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried with MgSO4
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-da59f178f753451d9c8f9b6c020ea1df
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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