4-Methylmorpholine → HCID 131714440, compound

HRID 1583844Notes

Reaction equation

HRID 1583844 reaction equation
[NH:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@@H:2]([C:4]([OH:6])=O)[CH3:3].CN1CCOCC1.C(Cl)(=O)C(C)(C)C.[NH:28]([CH3:43])[C@H:29]([C:34]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:35])[CH2:30][CH:31]([CH3:33])[CH3:32]>C(Cl)(Cl)Cl.O>[NH:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@@H:2]([C:4]([N:28]([CH3:43])[C@H:29]([C:34]([CH2:36][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)=[O:35])[CH2:30][CH:31]([CH3:32])[CH3:33])=[O:6])[CH3:3]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62493Pivaloyl chlorideHCID 637606BOC-D-alanineHCID 131714441HCID 131714441, compound

Product 1

HCID 131714440HCID 131714440, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent3×

Conditions

Temperature
-20 °C

Procedure

18.9 g (100 m mol) Boc-(D)-Ala-OH are dissolved in 250 ml chloroform and cooled with stirring to -20° C. 23.1 ml (21.2 g=210 m mol) N-methylmorpholine and 12.2 ml (12.0 g=100 m mol) pivaloyl chloride are then added and the whole stirred for 2 hours, still at -20° C. Anhydride formation is followed by means of IR control. When anhydride formation is complete 23.5 g (100 m mol) H-MeLeu-Bzl dissolved in 50 ml chloroform are added dropwise to the obtained reaction mixture at -20° C. and over a period of 5 minutes. Formation of the dipeptide is followed using thin-layer chromatography and IR-spectrometry. After 19 hours no further anhydride can be detected. The obtained reaction solution is poured onto 300 ml water and diluted with 300 ml chloroform. The organic phase is separated, washed with 100 ml water, dried over sodium sulphate, filtered and the solvent carefully evaporated off at max. 40° C. The obtained residue is recrystallised from hexane to yield the title compound: rotation, [α]D25 =-35.3° C. (c=1.05 m chloroform; M.P.=81° C.

Workup

  1. temperaturecooled
  2. stirringthe whole stirred for 2 hours, still at -20° C
  3. additionare added dropwise to the obtained reaction mixture at -20° C. and over a period of 5 minutes
  4. customThe obtained reaction solution
  5. customThe organic phase is separated
  6. washwashed with 100 ml water
  7. dry with materialdried over sodium sulphate
  8. filtrationfiltered
  9. customthe solvent carefully evaporated off at max
  10. custom40° C
  11. customThe obtained residue is recrystallised from hexane

Sources & evidence

ORD record
ord-e111b228356e4cfaac09879a67af634f
Source dataset
uspto-grants-1985_11
Patent number
US04554351

Reaction notes

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