HCID 117870535, compound → HCID 117870842, compound

HRID 530648Notes

Reaction equation

HRID 530648 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH:14](Br)[C:15]2[CH:16]=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.C(OCC)(=O)C.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:16]=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 1

HCID 117870535HCID 117870535, compound

Product 1

HCID 117870842HCID 117870842, compoundYield 88.6%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-2-[bromo-(6-methoxy-pyridin-3-yl)-methyl]-morpholine-4-carboxylic acid tert-butyl ester (290 mg, 0.75 mmol) was dissolved in methanol (5 mL) and hydrogenated at 0.25 bar in the presence of 50 mg 10% Pd/C. Reaction mixture was diluted with ethyl acetate and filtered through Dicalite. The filtrate was washed with 1M sodium hydroxide. The aqueous phase was extract 2 times with ethyl acetate. The combined organic phase was washed with brine, dried over MgSO4, filtered and concentrated to afford (R)-2-(6-Methoxy-pyridin-3-ylmethyl)-morpholine-4-carboxylic acid tert-butyl ester (205 mg, 88%) as a light yellow oil. Chiral HPLC (Chiralpak-AD) indicated that product was 98.3% pure. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.45 (s, 9H) 2.53-2.79 (m, 3H) 2.86-3.00 (m, 1H) 3.38-3.58 (m, 2H) 3.73-3.89 (m, 3H) 3.91 (s, 3H) 6.68 (d, J=8.33 Hz, 1H) 7.39-7.49 (m, 1H) 8.00 (d, J=2.15 Hz, 1H).

Workup

  1. customReaction mixture
  2. filtrationfiltered through Dicalite
  3. washThe filtrate was washed with 1M sodium hydroxide
  4. extractionThe aqueous phase was extract 2 times with ethyl acetate
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e77ad70c7583464192396e672bb3a1d7
Source dataset
uspto-grants-2016_05
Patent number
US09353096B2

Reaction notes

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