4-Methylmorpholine → HCID 131714443, compound

HRID 1583847Notes

Reaction equation

HRID 1583847 reaction equation
CN1CCOCC1.C(Cl)(=O)C(C)(C)C.[NH:15]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C@@H:16]([C:18]([N:20]([CH3:38])[C@H:21]([C:26]([N:28]([CH3:37])[C@H:29]([C:34](O)=[O:35])[CH2:30][CH:31]([CH3:33])[CH3:32])=[O:27])[CH2:22][CH:23]([CH3:25])[CH3:24])=[O:19])[CH3:17].[NH:46]([CH3:60])[C@H:47]([C:51]([CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:52])[CH:48]([CH3:50])[CH3:49].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[NH:15]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C@@H:16]([C:18]([N:20]([CH3:38])[C@H:21]([C:26]([N:28]([CH3:37])[C@H:29]([C:34]([N:46]([CH3:60])[C@H:47]([C:51]([CH2:53][C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1)=[O:52])[CH:48]([CH3:49])[CH3:50])=[O:35])[CH2:30][CH:31]([CH3:32])[CH3:33])=[O:27])[CH2:22][CH:23]([CH3:24])[CH3:25])=[O:19])[CH3:17]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 62493Pivaloyl chlorideHCID 516892Sodium BicarbonateHCID 13254983HCID 13254983, compoundHCID 131714444HCID 131714444, compound

Product 1

HCID 131714443HCID 131714443, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent3×

Conditions

Temperature
-20 °C

Procedure

3.48 ml (3.18 g=31.5 m mol) N-methylmorpholine and 1.86 ml (1.8 g=15.0 m mol) pivaloyl chloride are added to a solution of 6.65 g (15.0 m mol) BOC-(D)-Ala-MeLeu-Me-Leu-OH in 60 ml chloroform, pre-cooled to -20° C. Conversion to the anhydride is completed after stirring for 2 hours at -20° C. (IR control). 3.35 g (15.0 m mol) H-MeVal-Bzl in 50 ml chloroform are then added dropwise to the reaction mixture at -20° C. The progress of the reaction is followed by means of thin-layer chromatography and IR-spectrometry and is complete after 41/2 days. The obtained solution is poured onto 200 ml 1N sodium bicarbonate on a shaker, and diluted with 300 ml chloroform. After separation of the organic phase, the aqueous phase is extracted with a further 100 ml chloroform, the combined chloroform phases dried over sodium sulphate, filtered and evaporated. The residue is chromatographed on 600 g silica gel (0.063-0.2 mm) using 2% methanol in methylene chloride as eluant to yield the title compound: rotation, [α]D25 =-143.7° (c=0.9 in chloroform).

Workup

  1. custom2 days
  2. customAfter separation of the organic phase
  3. extractionthe aqueous phase is extracted with a further 100 ml chloroform
  4. dry with materialthe combined chloroform phases dried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is chromatographed on 600 g silica gel (0.063-0.2 mm)

Sources & evidence

ORD record
ord-523590a85472405e92b5a62626a0146e
Source dataset
uspto-grants-1985_11
Patent number
US04554351

Reaction notes

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