Morpholine, 4-[3-amino-5-(trifluoromethyl)benzoyl]- → 3-(Morpholin-4-ylmethyl)-5-(trifluoromethyl)aniline

HRID 1446701Notes

Reaction equation

HRID 1446701 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=O)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1>C1COCC1>[N:14]1([CH2:12][C:4]2[CH:3]=[C:2]([NH2:1])[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[CH:5]=2)[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1

Participants

3

Reactant 1

HCID 66876746Morpholine, 4-[3-amino-5-(trifluoromethyl)benzoyl]-

Product 1

HCID 219550073-(Morpholin-4-ylmethyl)-5-(trifluoromethyl)anilineYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Dissolve (3-amino-5-trifluoromethyl-phenyl)-morpholin-4-yl-methanone (1.2 g, 4.3 mmol) in THF and dropwise and add BH3-Me2S solution (6.5 mL, 13.1 mmol, 2M in THF). Stir at room temperature for 3 hours. Add another portion of BH3-Me2S solution (2.2 mL, 4.3 mmol, 2M in THF) and heat at 65° C. for 1.5 hours under nitrogen. Cool to room temperature and quench carefully with dropwise addition of 1 N HCl:water 1:1 (8 mL), stir for 30-60 minutes. Extract by EtOAc and wash with saturated aqueous NaHCO3 and aqueous saturated sodium chloride. Purification by silica gel column chromatography with gradient from 100% DCM to 6% MeOH in DCM to 5% (2N NH3 in MeOH)/in DCM, yielding the title compound (600 mg, 54% yield). LCMS (ES), m/z 261 (M+1).

Workup

  1. temperatureheat at 65° C. for 1.5 hours under nitrogen
  2. temperatureCool to room temperature
  3. customquench carefully with dropwise addition of 1 N HCl:water 1:1 (8 mL)
  4. stirringstir for 30-60 minutes
  5. extractionExtract by EtOAc
  6. washwash with saturated aqueous NaHCO3 and aqueous saturated sodium chloride
  7. customPurification by silica gel column chromatography with gradient from 100% DCM to 6% MeOH in DCM to 5% (2N NH3 in MeOH)/in DCM

Sources & evidence

ORD record
ord-93e829df4d3046379f283ac85ab16ecf
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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