Methanol → Trifluoroacetic acid

HRID 625492Notes

Reaction equation

HRID 625492 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:40]=[CH:41][CH:42]=1)[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]([CH2:18][CH3:19])[CH2:16][CH3:17])=[CH:11][C:10]=1[C:20]1[CH:21]=[C:22]([CH:37]=[CH:38][N:39]=1)[C:23]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=1)=[O:24])=[O:7].C(=O)([S:45][CH2:46][CH2:47][O:48][CH2:49][CH2:50][O:51][CH2:52][CH2:53][O:54][CH2:55][CH2:56][O:57][CH2:58][CH2:59][O:60][CH2:61][CH2:62][O:63][CH2:64][CH2:65][O:66][CH2:67][CH2:68][O:69][CH3:70])C.C[O-].[Na+].CO.[C:77]([OH:83])([C:79]([F:82])([F:81])[F:80])=[O:78]>CN(C=O)C.O>[C:77]([OH:83])([C:79]([F:82])([F:81])[F:80])=[O:78].[CH3:70][O:69][CH2:68][CH2:67][O:66][CH2:65][CH2:64][O:63][CH2:62][CH2:61][O:60][CH2:59][CH2:58][O:57][CH2:56][CH2:55][O:54][CH2:53][CH2:52][O:51][CH2:50][CH2:49][O:48][CH2:47][CH2:46][S:45][CH2:2][C:3]1[CH:4]=[C:5]([CH:40]=[CH:41][CH:42]=1)[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]([CH2:18][CH3:19])[CH2:16][CH3:17])=[CH:11][C:10]=1[C:20]1[CH:21]=[C:22]([CH:37]=[CH:38][N:39]=1)[C:23]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=1)=[O:24])=[O:7]

Participants

9

Reactant 5

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 10942334Sodium MethoxideHCID 66588101HCID 66588101, compoundHCID 86709219HCID 86709219, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 86709218HCID 86709218, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(2-(3-(chloromethyl)benzamido)-5-(diethylamino)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide 143a (715 mg, 1.2 mmol) and S-2,5,8,11,14,17,20,23-octaoxapentacosan-25-yl ethanethioate 135c.3 (590 mg, 1.33 mmol) in DMF (10 mL) was added 4.3 M NaOMe in MeOH (0.37 mL, 1.6 mmol) and stirred at room temperature for 15 minutes. The reaction mixture was added to water (35 mL) and extracted with DCM (3×50 mL). The combined organic layers were washed with water (25 mL), dried (Na2SO4) and concentrated at reduced pressure. The residue was purified by flash chromatography on silica gel (1% to 5% MeOH in DCM). The purified product was dissolved in 50% ACN/water and TFA (410 mg, 3.6 mmol) was added. Lyophilization gave a TFA salt of the title compound (1.34 g) as a light yellow oil. MS (ES, m/z): 959.4 [M+H]+.

Workup

  1. extractionextracted with DCM (3×50 mL)
  2. washThe combined organic layers were washed with water (25 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated at reduced pressure
  5. customThe residue was purified by flash chromatography on silica gel (1% to 5% MeOH in DCM)
  6. dissolutionThe purified product was dissolved in 50% ACN/water

Sources & evidence

ORD record
ord-8eb85c2942e7489eb463abd4ce84352a
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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