4-Methylmorpholine → HCID 131714442, compound

HRID 1583846Notes

Reaction equation

HRID 1583846 reaction equation
CN1CCOCC1.[NH:8]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@@H:9]([C:11]([N:13]([CH3:22])[C@H:14]([C:19]([OH:21])=O)[CH2:15][CH:16]([CH3:18])[CH3:17])=[O:12])[CH3:10].C(Cl)(=O)C(C)(C)C.[NH:37]([CH3:52])[C@H:38]([C:43]([CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:44])[CH2:39][CH:40]([CH3:42])[CH3:41]>C(Cl)(Cl)Cl.O>[NH:8]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@@H:9]([C:11]([N:13]([CH3:22])[C@H:14]([C:19]([N:37]([CH3:52])[C@H:38]([C:43]([CH2:45][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)=[O:44])[CH2:39][CH:40]([CH3:41])[CH3:42])=[O:21])[CH2:15][CH:16]([CH3:17])[CH3:18])=[O:12])[CH3:10]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62493Pivaloyl chlorideHCID 13254981N-(tert-Butoxycarbonyl)-D-alanyl-N-methyl-L-leucineHCID 131714441HCID 131714441, compound

Product 1

HCID 131714442HCID 131714442, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent2×

Conditions

Temperature
-20 °C

Procedure

17.9 ml (16.4 g=162.4 m mol) N-methylmorpholine are added to a solution of 24.5 g (77.3 m mol) BOC-(D)-Ala-MeLeu-OH dissolved in 200 ml chloroform and the whole is cooled to -20° C. 9.5 ml (9.27 g=77.3 m mol) pivaloyl chloride are then added over 5 minutes and the reaction mixture stirred for 90 minutes, still at -20° C. Anhyride formation is followed by means of IR control and when complete a solution of 18.2 g (77.3 m mol) H-MeLeu-Bzl in 50 ml chloroform is added dropwise at -20° within 5 minutes. A reaction period of 18 hours at -20° C. is required until no more anhydride is present. The obtained solution is poured onto 300 ml water and is extracted in a separating funnel after first diluting with a further 300 ml chloroform. The aqueous phase is extracted with 300 ml chloroform, the combined organic phases dried over sodium sulphate, filtered and evaporated. The residue is chromatographed on 1 kg silica gel (0.063-0.24 mm) using 2% methanol in methylene chloride as eluant to yield the title compound: rotation, [α]D25 =-101.3° (c=0.9 in chloroform).

Workup

  1. additionis added dropwise at -20° within 5 minutes
  2. customA reaction period of 18 hours at -20° C.
  3. extractionis extracted in a separating funnel
  4. additionafter first diluting with a further 300 ml chloroform
  5. extractionThe aqueous phase is extracted with 300 ml chloroform
  6. dry with materialthe combined organic phases dried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue is chromatographed on 1 kg silica gel (0.063-0.24 mm)

Sources & evidence

ORD record
ord-01e165922ea148c3a1d9480b9d887cec
Source dataset
uspto-grants-1985_11
Patent number
US04554351

Reaction notes

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