Isobutyraldehyde → Methyl 5-[{4-[(4-butylphenyl)ethynyl]benzyl)(isobutyl)amino]-2-fluorobenzoate

HRID 551979Notes

Reaction equation

HRID 551979 reaction equation
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:31]=[CH:30][C:16]([CH2:17][NH:18][C:19]3[CH:20]=[CH:21][C:22]([F:29])=[C:23]([CH:28]=3)[C:24]([O:26][CH3:27])=[O:25])=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[CH:32](=O)[CH:33]([CH3:35])[CH3:34].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C([O-])(O)=O.[Na+]>ClCCCl>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]#[C:12][C:13]2[CH:14]=[CH:15][C:16]([CH2:17][N:18]([CH2:32][CH:33]([CH3:35])[CH3:34])[C:19]3[CH:20]=[CH:21][C:22]([F:29])=[C:23]([CH:28]=3)[C:24]([O:26][CH3:27])=[O:25])=[CH:30][CH:31]=2)=[CH:9][CH:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 6561IsobutyraldehydeHCID 516892Sodium BicarbonateHCID 2724942TriacetoxyborohydrideHCID 11452740Methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-fluorobenzoate

Product 1

HCID 57554537Methyl 5-[{4-[(4-butylphenyl)ethynyl]benzyl)(isobutyl)amino]-2-fluorobenzoateYield 19%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-fluorobenzoate (300 mg; 0.72 mmol) in DCE (15 mL) were added isobutyraldehyde (Aldrich, 0.16 ml, 1.81 mmol) and triacetoxyborohydride (229 mg; 1.08 mmol). The reaction mixture was stirred at 60° C. under N2 atmosphere for 4 hours. The mixture was poured into NaHCO3 (100 mL), then the product was extracted with DCM (2×100 mL), washed with brine (100 mL), dried over magnesium sulfate and filtrated. The solvents were removed under reduced pressure. Purification of this crude by flash chromatography on silicagel (c-Hex/EtOAc, gradient 8:2 to 5:5 to 3:7) then by HPLC preparative with a X-Terra column gave 62 mg (19%) of the title compound as a brown oil. HPLC: 6.19 min (purity=96.4%), LC/MS: M+(ESI): 472.4. 1H NMR (CDCl3) δ: 7.44 (d, J=5.6 Hz, 2H), 7.41 (d, J=5.3 Hz, 2H), 7.25 (m, 1H), 7.14 (t, J=7.5 Hz, 4H), 6.94 (t, J=9.6 Hz, 1H), 6.80 (m, 1H), 4.57 (s, 2H), 3.90 (s, 3H), 3.45 (m, 1H), 3.25 (d, J=7.2 Hz, 2H), 2.61 (t, J=7.7 Hz, 2H), 2.05 (m, 1H), 1.60 (m, 2H), (s, J=7.4 Hz, 2H), 0.95 (m, 9H).

Workup

  1. extractionthe product was extracted with DCM (2×100 mL)
  2. washwashed with brine (100 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltrated
  5. customThe solvents were removed under reduced pressure
  6. customPurification of this crude by flash chromatography on silicagel (c-Hex/EtOAc, gradient 8:2 to 5:5 to 3:7)

Sources & evidence

ORD record
ord-e3925937af4c4bff934fe3aeb979a1a8
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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