Hydrochloric Acid → (2R,6R)-2-Methyl-6-(trifluoromethyl)morpholine hydrochloride

HRID 922775Notes

Reaction equation

HRID 922775 reaction equation
C([N:8]1[CH2:13][C@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C@H:10]([CH3:18])[CH2:9]1)C1C=CC=CC=1.[ClH:19]>CO.[Pd]>[ClH:19].[CH3:18][C@H:10]1[O:11][C@@H:12]([C:14]([F:16])([F:15])[F:17])[CH2:13][NH:8][CH2:9]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 588470294-Benzyl-cis-2-methyl-6-(trifluoromethyl)morpholine

Product 1

HCID 89545142(2R,6R)-2-Methyl-6-(trifluoromethyl)morpholine hydrochlorideYield 103%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of (2R,6R)-4-benzyl-2-methyl-6-(trifluoromethyl)morpholine (4-5, 4.1 g, 15.81 mmol) in MeOH (80 ml) was added concentrated HCl (6.6 ml, 79 mmol). This mixture was transferred to a Parr bottle containing 10% Pd/C (1.7 g, 1.597 mmol). The mixture was hydrogenated (45 psi) overnight. The mixture was filtered through a pad of Celite washing with MeOH then concentrated. The residue was taken up in MeOH and concentrated (3×) to afford (2R,6R)-2-methyl-6-(trifluoromethyl)morpholine hydrochloride (4-6, 3.34 g, 103%) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 4.59 (bs, 2H); 4.27 (bs, 2H); 3.01 (bs, 1H); 2.79 (bs, 1H); 1.33 (s, 3H).

Workup

  1. custom(45 psi) overnight
  2. filtrationThe mixture was filtered through a pad of Celite
  3. washwashing with MeOH
  4. concentrationthen concentrated
  5. concentrationconcentrated (3×)

Sources & evidence

ORD record
ord-6eb084ddd2894b3dac138e3390079ee5
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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