4-Methylmorpholine → (S)-2-(Boc-amino)-3-cyclohexyl-N-methoxy-N-methylpropanamide

HRID 58832

Reaktionsgleichung

Reaktionsgleichung von HRID 58832
Cl.[CH3:2][N:3](C)[OH:4].[CH2:6](N(CC)CC)C.[C:13]([O:17][C:18]([NH:20][C@@H:21]([CH2:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[C:22]([OH:24])=O)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(OC(Cl)=O)C(C)C.CN1CCOCC1.CN(C)O>C(Cl)Cl.C1COCC1>[CH:26]1([CH2:25][C@H:21]([NH:20][C:18](=[O:19])[O:17][C:13]([CH3:14])([CH3:15])[CH3:16])[C:22]([N:3]([O:4][CH3:6])[CH3:2])=[O:24])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1

Komponenten

9

Edukt 6

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 27969N,N-dimethylhydroxylamine hydrochlorideHCID 27970DimethylhydroxylamineHCID 62365Isobutyl chloroformateHCID 10588189(2S)-2-(((tert-butoxy)carbonyl)amino)-3-cyclohexylpropanoic acid

Produkt 1

HCID 10495486(S)-2-(Boc-amino)-3-cyclohexyl-N-methoxy-N-methylpropanamideAusbeute 105,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of dimethylhydroxylamine hydrochloride (3.98 g, 40.6 mmol) in DCM (50 mL) at 0° C. was added triethylamine (5.43 mL, 41.9 mmol). In a separate flask (S)-2-((tert-butoxycarbonyl)amino)-3-cyclohexylpropanoic acid (10.0 g, 36.9 mmol) in DCM (50 mL) and THF (50 mL) was cooled to 0° C. and isobutylchloroformate (4.83 mL, 36.9 mmol) was added followed by N-methylmorpholine (4.06 mL, 36.9 mmol). After 1 h it was added to the dimethylhydroxylamine mixture. The combined mixture was allowed to warm to ambient temperature over 16 h at which time it was quenched with water, washed with sodium bicarbonate (sat.), extracted with EtOAc (2×), washed with brine, dried with sodium sulfate, filtered, and concentrated. (S)-tert-Butyl (3-cyclohexyl-1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate (12.2 g) was provided as a colorless oil that was carried forward without further purification. MS (EI) for C16H30N2O4, found 215.3 [M-Boc]+.

Aufarbeitung

  1. customwas quenched with water
  2. washwashed with sodium bicarbonate (sat.)
  3. extractionextracted with EtOAc (2×)
  4. washwashed with brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-e82ad99134884c27bdbe5bbb99139203
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434761B2

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