Benzylamine → N-benzyl-O-methyl-N2-trityl-D-serinamide

HRID 389381Notes

Reaction equation

HRID 389381 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([C:25](O)=[O:26])[NH:5][C:6]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CN1CCOCC1.C(OC(Cl)=O)C(C)C.[CH2:43]([NH2:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>O1CCCC1.C(OCC)(=O)C>[CH2:43]([NH:50][C:25](=[O:26])[C@@H:4]([CH2:3][O:2][CH3:1])[NH:5][C:6]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 57734153O-methyl-N-trityl-D-serine

Product 1

HCID 54752467N-benzyl-O-methyl-N2-trityl-D-serinamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of Example 2 product (i.e., O-methyl-N-trityl-D-serine, 50 g) in tetrahydrofuran (500 ml), N-methyl morpholine (20.9 g) was added at −15° C. in 5-10 minutes. The reaction mixture was stirred for 15 minutes and then isobutylchloroformate (18.8 g) diluted with tetrahydrofuran was added to it at −15° C. under nitrogen atmosphere in 15-20 minutes. The solution was stirred for 15 minutes and benzyl amine (14.7 g) was added to it at −15° C. in 15 minutes. The solution was allowed to cool to room temperature and stirred for 2 hours. The solvent was recovered from the solution. Dichloromethane (250 ml) was added to the crude product and stirred for 5 minutes to dissolve. The dichloromethane layer was washed or stirred for 5 minutes with water (250 ml). The layers were separated and the dichloromethane layer was again washed with 5% NaHCO3 (250 ml). The layers were separated and then the dichloromethane layer was sequentially washed with 5% citric acid solution (250 ml) and then with water (250 ml). The solvent was recovered at 40° C. to 45° C. to get oil. Ethyl acetate was added to the oil and the mixture was heated to 60° C. to 65° C. to dissolve. The clear solution so formed was cooled up to room temperature and then hexanes (350 ml) were added to it. It was stirred for 1 hour at room temperature, filtered and then dried to get compound of Formula Va. Yield=30 gm.

Workup

  1. additionwas added to it at −15° C. under nitrogen atmosphere in 15-20 minutes
  2. stirringThe solution was stirred for 15 minutes
  3. stirringstirred for 2 hours
  4. customThe solvent was recovered from the solution
  5. additionDichloromethane (250 ml) was added to the crude product
  6. stirringstirred for 5 minutes
  7. dissolutionto dissolve
  8. washThe dichloromethane layer was washed
  9. stirringstirred for 5 minutes with water (250 ml)
  10. customThe layers were separated
  11. washthe dichloromethane layer was again washed with 5% NaHCO3 (250 ml)
  12. customThe layers were separated
  13. washthe dichloromethane layer was sequentially washed with 5% citric acid solution (250 ml)
  14. customThe solvent was recovered at 40° C. to 45° C.
  15. customto get oil
  16. temperaturethe mixture was heated to 60° C. to 65° C.
  17. dissolutionto dissolve
  18. customThe clear solution so formed
  19. temperaturewas cooled up to room temperature
  20. stirringIt was stirred for 1 hour at room temperature
  21. filtrationfiltered
  22. customdried
  23. customto get compound of Formula Va

Sources & evidence

ORD record
ord-def62752c9fd4a9f8dba6bf344db7c40
Source dataset
uspto-grants-2013_02
Patent number
US08378142B2

Reaction notes

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