Trifluoroacetic acid → [4-Fluoro-3-(3-morpholin-4-ylprop-1-ynyl)phenyl]-methylamine

HRID 2211665Notes

Reaction equation

HRID 2211665 reaction equation
C(OC(NC[C:10]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]([C:17]#[C:18][CH2:19]O)[CH:11]=1)=O)(C)(C)C.C[N+:22]1([O-])[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.[NH:29]1CCOC[CH2:30]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(O)(C(F)(F)F)=O>C(Cl)Cl.C([O-])(O)=O.[Na+].CCC[N+](CCC)(CCC)CCC.[O-][Ru](=O)(=O)=O>[F:16][C:13]1[CH:14]=[CH:15][C:10]([NH:29][CH3:30])=[CH:11][C:12]=1[C:17]#[C:18][CH2:19][N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8083MorpholineHCID 82029Methyl morpholine oxideHCID 5049666Sodium triacetoxyborohydrideHCID 131725909(Tert-butoxy)-n-{[4-fluoro-3-(3-hydroxyprop-1-ynyl)phenyl]methyl}carboxamide

Product 1

HCID 21961413[4-Fluoro-3-(3-morpholin-4-ylprop-1-ynyl)phenyl]-methylamine

Reagents, catalysts & solvents 3

HCID 178419074HCID 178419074, compoundCatalystHCID 6344DichloromethaneSolvent3×HCID 516892Sodium BicarbonateSolvent

Procedure

To a mixture of (tert-butoxy)-N-{[4-fluoro-3-(3-hydroxyprop-1-ynyl)phenyl]methyl}carboxamide (0.23 g, 0.82 mmol) (Step B) and NMO (0.14 g, 1.3 mmol) was added catalytic amount of TPAP. The resulting mixture was stirred for 1 h at RT, then filtered over a short pad of SiO2 and concentrated. To a solution of the residue and morpholine (0.1 mL, 1.2 mmol) in CH2Cl2 was added excess NaBH(OAc)3. The resulting solution was stirred for 16 h, diluted with CH2Cl2 and saturated aq. NaHCO3 solution. The organic layer was separated, dried over Na2SO4, and concentrated. The residue was purified by SiO2 chromatography to give a colorless oil, which was dissolved in 5 mL of CH2Cl2. To the organic solution was added TFA (2 mL). The resulting solution was stirred for 1 h at RT, then concentrated. The residue was diluted with CH2Cl2 and saturated aq. NaHCO3 solution. The organic layer was separated, dried over Na2SO4, and concentrated to give the title compound. MS (ES+): 249 (M+H)+; (ES−): 247. Calc'd C14H17FN2O-248.30.

Workup

  1. filtrationfiltered over a short pad of SiO2
  2. concentrationconcentrated
  3. stirringThe resulting solution was stirred for 16 h
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by SiO2 chromatography
  8. customto give a colorless oil, which
  9. stirringThe resulting solution was stirred for 1 h at RT
  10. concentrationconcentrated
  11. additionThe residue was diluted with CH2Cl2 and saturated aq. NaHCO3 solution
  12. customThe organic layer was separated
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-881fb1fc18fb4b91834ed3f8f47deab9
Source dataset
uspto-grants-2006_09
Patent number
US07101868B2

Reaction notes

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