Water → (2R)-N-cyclopropyl-N-[4-methoxy-3-(3-methoxypropoxy)benzyl]morpholine-2-carboxamide

HRID 872004Notes

Reaction equation

HRID 872004 reaction equation
Cl.O1CCOCC1.C(OC([N:15]1[CH2:20][CH2:19][O:18][C@@H:17]([C:21]([N:23]([CH:39]2[CH2:41][CH2:40]2)[CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[C:27]([O:33][CH2:34][CH2:35][CH2:36][O:37][CH3:38])[CH:26]=2)=[O:22])[CH2:16]1)=O)(C)(C)C.O>C(Cl)(Cl)Cl>[CH:39]1([N:23]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[C:27]([O:33][CH2:34][CH2:35][CH2:36][O:37][CH3:38])[CH:26]=2)[C:21]([C@@H:17]2[O:18][CH2:19][CH2:20][NH:15][CH2:16]2)=[O:22])[CH2:41][CH2:40]1

Participants

5

Reactant 3

HCID 962WaterHCID 204431481,4-Dioxane hydrochlorideHCID 59494725tert-butyl(2R)-2-({cyclopropyl[4-methoxy-3-(3-methoxypropoxy)benzyl]amino}carbonyl)morpholin-4-carboxylate

Product 1

HCID 67541956(2R)-N-cyclopropyl-N-[4-methoxy-3-(3-methoxypropoxy)benzyl]morpholine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

4N HCl/dioxane (1 ml) was added under ice cooling to (2R)-2-({cyclopropyl[4-methoxy-3-(3-methoxypropoxy)benzyl]amino}carbonyl)morpholin-4-carboxylic acid tert-butyl ester (a compound of Reference Example 8, 368 mg) dissolved in chloroform (4 ml), and the mixture was stirred at room temperature for 2 hours. Water was added to the mixture under ice cooling and the organic layer was separated. The aqueous layer was extracted with chloroform after being adjusted to pH 9 by addition of a saturated aqueous solution of sodium bicarbonate. The organic layer was washed with a saturated brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by NH-silica gel column chromatography (eluting solvent; n-hexane:ethyl acetate=1:1 to ethyl acetate only) to give (2R)—N-cyclopropyl-N-[4-methoxy-3-(3-methoxypropoxy)benzyl]morpholine-2-carboxamide (230 mg) as a colorless oil.

Workup

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was extracted with chloroform
  3. additionafter being adjusted to pH 9 by addition of a saturated aqueous solution of sodium bicarbonate
  4. washThe organic layer was washed with a saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by NH-silica gel column chromatography (
  8. washeluting solvent

Sources & evidence

ORD record
ord-9a4eedc2b964432186d23f3f2234f5d2
Source dataset
uspto-grants-2015_03
Patent number
US08975252B2

Reaction notes

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