Sodium Bicarbonate → Methyl 2-fluoro-5-[{4-[(4-fluorophenyl)ethynyl]benzyl)-(hexyl)amino]benzoate

HRID 551967Notes

Reaction equation

HRID 551967 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:9]([NH:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]#[C:27][C:28]2[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=2)=[CH:22][CH:21]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[F:1][C:2]1[CH:11]=[CH:10][C:9]([N:12]([CH2:32][C:31]2[CH:30]=[CH:29][C:28]([C:27]#[C:26][C:23]3[CH:22]=[CH:21][C:20]([F:19])=[CH:25][CH:24]=3)=[CH:35][CH:34]=2)[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 43715358Methyl 2-fluoro-5-(hexylamino)benzoateHCID 454901144-[2-(4-Fluorophenyl)ethynyl]benzaldehyde

Product 1

HCID 57554486Methyl 2-fluoro-5-[{4-[(4-fluorophenyl)ethynyl]benzyl)-(hexyl)amino]benzoateYield 32%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 2-fluoro-5-(hexylamino)benzoate (270 mg; 1.07 mmol) and 4-[(4-fluorophenyl)ethynyl]benzaldehyde (358 mg; 1.60 mmol, intermediate which may be obtained according to methods disclosed in EP03103780.7) in anhydrous DCE (15 mL) was added sodium triacetoxyborohydride (678 mg; 3.20 mmol) at rt. The reaction mixture was then heated at 50° C. for 14 h. It was then poured into a solution of saturated NaHCO3 and extracted twice with DCM. The combined organic phases were then washed with brine, dried over MgSO4, filtrated and concentrated. The crude brown oil (652 mg) was purified by preparative HPLC using a X-Terra column to give 158 mg (32%) of the title compound as a beige powder. HPLC, Rt: 6.01 min (purity: 96.5%), LC/MS, M+(ESI): 462.2, 1H NMR: (CDCl3) δ: 7.46 (m, 2H), 7.41 (d, J=8.3 Hz, 2H), 7.37 (m, 1H), 7.13 (d, J=7.9 Hz, 2H), 6.94-7.05 (m, 4H), 4.52 (s, 2H), 3.90 (s, 3H), 3.42 (t, J=7.7 Hz, 2H), 1.56 (m, 2H), 1.26 (m, 6H), 0.85 (t, J=6.6 Hz, 3H).

Workup

  1. extractionextracted twice with DCM
  2. washThe combined organic phases were then washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltrated
  5. concentrationconcentrated
  6. customThe crude brown oil (652 mg) was purified by preparative HPLC

Sources & evidence

ORD record
ord-bdbd0bd98cfe4bb886f4b6f6e72d5cc1
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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