Morpholine → HCID 66600229, compound

HRID 1621544Notes

Reaction equation

HRID 1621544 reaction equation
Br[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([F:9])=[N:7][CH:8]=1.[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.C(N(CC)CC)C>C1COCC1>[F:9][C:6]1[N:7]=[CH:8][C:3]([CH2:2][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][CH:5]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 220506385-(Bromomethyl)-2-fluoropyridine

Product 1

HCID 66600229HCID 66600229, compoundYield 58.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-(bromomethyl)-2-fluoropyridine (26.000 g, 137 mmol) in THF (30 mL) was cooled to −30° C. and morpholine (17.88 mL, 205 mmol) was slowly added. After min, triethylamine (57.2 mL, 410 mmol) was slowly added. Following addition, the cooling bath was removed and the mixture was allowed to warm to ambient temperature. After 30 min, the mixture was filtered through a fine-fritted funnel and the filtrate was concentrated to give an orange oil. The crude material was purified by chromatography through a Thompson Instruments pre-packed silica gel (330 gram) column eluting with a gradient of 0% to 100% EtOAc in hexane over 50 min to give 4-((6-fluoropyridin-3-yl)methyl)morpholine (15.767 g, 80 mmol, 58.7% yield) as an orange oil. 1H NMR (400 MHz, CDCl3) δ 8.13 (s, 1H); 7.79 (td, J=8.07, 2.45 Hz, 1H); 6.90 (dd, J=8.31, 2.84 Hz, 1H); 3.67-3.72 (m, 4H); 3.49 (s, 2H); 2.39-2.48 (m, 4H). m/z (ESI, +ve ion) 197.1 (M+H)+.

Workup

  1. additionaddition
  2. customthe cooling bath was removed
  3. filtrationthe mixture was filtered through a fine-fritted funnel
  4. concentrationthe filtrate was concentrated
  5. customto give an orange oil
  6. customThe crude material was purified by chromatography through a Thompson Instruments pre-packed silica gel (330 gram) column
  7. washeluting with a gradient of 0% to 100% EtOAc in hexane over 50 min

Sources & evidence

ORD record
ord-f5ae75a3deec4bf9aa0426318c618d6a
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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