4-Methylmorpholine → HCID 14599440, compound

HRID 1638757Notes

Reaction equation

HRID 1638757 reaction equation
[C:1]([NH:8][C@@H:9]([C:11]([OH:13])=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[CH3:30][O:31][C:32](=[O:39])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][NH2:38]>C(Cl)Cl>[NH:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[C@@H:9]([C:11]([NH:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][C:32]([O:31][CH3:30])=[O:39])=[O:13])[CH3:10]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 637606BOC-D-alanineHCID 11499324Methyl 6-aminohexanoate hydrochloride

Product 1

HCID 14599440HCID 14599440, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Boc-(D)-alanine (5.1 g, 26.9 mmol) in 100 ml of methylene chloride (CH2Cl2) was cooled to 0° C. and 5.9 ml (53.8 mmol) of N-methylmorpholine (NMM) were added. After cooling this vigorously stirred solution to -78° C., 3.5 ml (26.9 mmol) of isobutylchloroformate (IBCF) were added to this reaction which was run entirely under an Ar atmosphere. The mixture was allowed to warm slowly to 20° before it was again cooled to -78° C. and 4.9 g (26.9 mmol) of 6-aminohexanoic acid methylester hydrochloride were added in a single portion. Following warming this mixture to room temperature, it was allowed to stir 25 hour (h). Precipitated N-methylmorpholine hydrochloride was filtered off and the filtrate, after diluting with CH2Cl2 (200 ml), was washed 3×100 ml of 0.5N potassium bisulfate (KHSO4). The combined aqueous washes were extracted with a 100 ml portion of CH2Cl2 and the combined organics were washed 1×75 ml of brine, dried over Na2SO4 (anhy.), and stripped of all solvent under reduced pressure. By thin layer chromatography (10% ethanol (EtOH)/chloroform (CHCl3)) the yellow liquid title product was essentially one spot and used in subsequent reactions without further purification. Optical rotation [α]D +21.5° and +93.7° (365 nm) CHCl3. NMR shift of the (D)Ala methyl=1.34δ (CDCl3).

Workup

  1. temperatureto warm slowly to 20° before it
  2. temperaturewas again cooled to -78° C.
  3. temperatureFollowing warming this mixture to room temperature
  4. filtrationPrecipitated N-methylmorpholine hydrochloride was filtered off
  5. additionthe filtrate, after diluting with CH2Cl2 (200 ml)
  6. washwas washed 3×100 ml of 0.5N potassium bisulfate (KHSO4)
  7. extractionThe combined aqueous washes were extracted with a 100 ml portion of CH2Cl2
  8. washthe combined organics were washed 1×75 ml of brine
  9. dry with materialdried over Na2SO4 (anhy.)
  10. customused in subsequent reactions without further purification
  11. customOptical rotation [α]D +21.5° and +93.7° (365 nm) CHCl3

Sources & evidence

ORD record
ord-4c4e53463b984b94a9d178560ffe0761
Source dataset
uspto-grants-1989_11
Patent number
US04880829

Reaction notes

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