4-Methylmorpholine → N-(carbobenzyloxy)-3-(2-thienyl)-L-alanine-tert butylamide

HRID 1457180Notes

Reaction equation

HRID 1457180 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]([C:19]([OH:21])=O)[CH2:13][C:14]1[S:15][CH:16]=[CH:17][CH:18]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC([NH:32][C@H:33]([C:40](O)=O)[CH2:34]C1SC=CC=1)=O)C1C=CC=CC=1.[CH3:43]N1CCOCC1.C(OC(Cl)=O)C(C)C>C1COCC1>[C:33]([NH:32][C:19](=[O:21])[C@H:12]([CH2:13][C:14]1[S:15][CH:16]=[CH:17][CH:18]=1)[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])([CH3:40])([CH3:43])[CH3:34]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 128068302-{[(Benzyloxy)carbonyl]amino}-3-(thiophen-2-yl)propanoic acidHCID 53725744(2S)-2-Amino-3-(thien-2-yl)propanoic acid, N-CBZ protected

Product 1

HCID 22858355N-(carbobenzyloxy)-3-(2-thienyl)-L-alanine-tert butylamideYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Into a 500 ml flask was placed 8.06 g of the subtitled compound of Example A, N-(Benzyloxycarbonyl)-3-(2-thienyl)-L-alanine, in 130 ml of THF. The compound was cooled to 0° C. N-Methylmorpholine (4.23 ml) was added, followed by isobutylchloroformate (4-04 ml) over two minutes. The mixture was stirred for 15-20 minutes, and 3.74 ml of t-butylamire was added. The bath was removed, and the mixture was stirred at room temperature for two hours. The mixture was concentrated on rotovap, and the residue was taken up in ethyl acetate. The residue was washed successively with H2O, HCl, and saturated NaHCO3 solution. The organics were separated and dried with Na2SO4, filtered, and concentrated to an oil. The oil was dissolved in 100 ml hot hexane and cooled in a refrigerator overnight to give a solid. The hexane was decanted, followed by drying to yield a solid of 9.25 g N-(carbobenzyloxy)-3-(2-thienyl)-L-alanine-tert-butylamide (97% yield).

Workup

  1. customInto a 500 ml flask was placed
  2. addition3.74 ml of t-butylamire was added
  3. customThe bath was removed
  4. stirringthe mixture was stirred at room temperature for two hours
  5. concentrationThe mixture was concentrated on rotovap
  6. washThe residue was washed successively with H2O, HCl, and saturated NaHCO3 solution
  7. customThe organics were separated
  8. dry with materialdried with Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to an oil
  11. dissolutionThe oil was dissolved in 100 ml hot hexane
  12. temperaturecooled in a refrigerator overnight
  13. customto give a solid
  14. customThe hexane was decanted
  15. customby drying

Sources & evidence

ORD record
ord-3faab1a0ed1b4913857c2c15c4dc1efd
Source dataset
uspto-grants-1998_12
Patent number
US05846993

Reaction notes

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