Acetic Acid → Methyl 2-fluoro-5-[(hexylamino)methyl]benzoate

HRID 551988Notes

Reaction equation

HRID 551988 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([CH:10]=O)[CH:7]=[CH:6][C:5]=1[F:12].[CH2:14]([NH2:20])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C(O)(=O)C.C([O-])(O)=O.[Na+]>ClCCCl>[F:12][C:5]1[CH:6]=[CH:7][C:8]([CH2:10][NH:20][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[CH:9][C:4]=1[C:3]([O:2][CH3:1])=[O:13]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8102HexylamineHCID 516892Sodium BicarbonateHCID 2724942TriacetoxyborohydrideHCID 24971957Methyl 2-fluoro-5-formylbenzoate

Product 1

HCID 57554492Methyl 2-fluoro-5-[(hexylamino)methyl]benzoateYield 63%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To solution of 2-fluoro-5-formylbenzoic acid methyl ester (1.0 g; 5.49 mmol) in anhydrous DCE (50 mL) were added hexylamine (Aldrich, 0.87 mL; 6.59 mmol), triacetoxyborohydride (1.74 g; 8.24 mmol) and acetic acid (0.47 mL; 8.24 mmol). The resulting mixture was stirred at room temperature under N2 atmosphere for 5 hours. The mixture was poured into a saturated solution of NaHCO3 and extracted with DCM (2×200 mL). The combined organic layers were washed with brine, dried over magnesium sulfate, filtrated and the solvent was removed under reduced pressure. Purification by flash chromatography on silica gel (DCM/MeOH/NH4OH, 98:2:0.1) gave 920 mg (63%) of the title compound as a yellow cream. HPLC, Rt: 2.34 min (purity=94.9%), LC/MS: M+(ESI): 268.1, 1H NMR (CDCl3) δ: 7.8 (dd, J=2.2, 8.2 Hz, 1H), 7.42 (m, 1H), 7.00 (dd, J=8.2, 2.2 Hz, 1H), 3.91 (s, 3H), 3.76 (s, 2H), 2.58 (t, J=7.1 Hz, 2H), 1.46 (qt, J=6.7 Hz, 2H), 1.22 (m, 6H), 0.86 (t, J=6.7 Hz, 3H).

Workup

  1. extractionextracted with DCM (2×200 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltrated
  5. customthe solvent was removed under reduced pressure
  6. customPurification by flash chromatography on silica gel (DCM/MeOH/NH4OH, 98:2:0.1)

Sources & evidence

ORD record
ord-76ba4c169b524b92b22e95a5d536be01
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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