Diisopropylethylamine → 2-methoxy-N-[phenyl-(3-pyrrolidin-1-yl-oxetan-3-yl)-methyl]-4,6-bis-trifluoromethyl-benzamide

HRID 560218

Reaction equation

HRID 560218 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[C:8]([O:16][CH3:17])[C:4]=1[C:5](O)=[O:6].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[C:53]1([CH:59]([NH2:69])[C:60]2([N:64]3[CH2:68][CH2:67][CH2:66][CH2:65]3)[CH2:63][O:62][CH2:61]2)[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>CN(C)C=O>[CH3:17][O:16][C:8]1[CH:9]=[C:10]([C:12]([F:13])([F:14])[F:15])[CH:11]=[C:3]([C:2]([F:1])([F:18])[F:19])[C:4]=1[C:5]([NH:69][CH:59]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:60]1([N:64]2[CH2:65][CH2:66][CH2:67][CH2:68]2)[CH2:63][O:62][CH2:61]1)=[O:6]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27412872-Methoxy-4,6-bis(trifluoromethyl)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59197932C-Phenyl-C-(3-pyrrolidin-1-yl-oxetan-3-yl)-methylamine2×

Product 1

HCID 461789612-methoxy-N-[phenyl-(3-pyrrolidin-1-yl-oxetan-3-yl)-methyl]-4,6-bis-trifluoromethyl-benzamideYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2,4-Bis(trifluoromethyl)-6-methoxybenzoic acid (155 mg, 0.538 mmol) was dissolved in 2 mL dimethylformamide. N,N-Diisopropyl ethyl amine (78 mg, 0.605 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (205 mg, 0.539 mmol) were added. After 5 minutes of stirring at room temperature C-phenyl-C-(3-pyrrolidin-1-yl-oxetan-3-yl)-methylamine (intermediate B) (125 mg, 0.539 mmol) in 2 mL dimethylformamide was added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated off. The residue was taken up in 2N sodium carbonate solution and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (heptane/ethyl acetate 1:0-1:1) yielded 2-methoxy-N-[phenyl-(3-pyrrolidin-1-yl-oxetan-3-yl)-methyl]-4,6-bis-trifluoromethyl-benzamide as an off-white solid (173 mg, 64%), MS: m/e=503.2 [(M+H)+].

Workup

  1. additionwas added
  2. customThe solvent was evaporated off
  3. extractionethyl acetate and was extracted three times with ethyl acetate
  4. customThe combined organic phases were dried on sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification of the residue by flash chromatography on silica gel (heptane/ethyl acetate 1:0-1:1)

Sources & evidence

ORD record
ord-794e7b21d4d44e98a0a40b7aaad0f9ed
Source dataset
uspto-grants-2011_11
Patent number
US08063098B2

Linked notes

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