Dichloromethane → 5-{[4-(4-Butyl-phenylethynyl)-benzyl]-cyclopentylmethylamino}-2-fluoro-benzoic acid methyl ester

HRID 551952Notes

Reaction equation

HRID 551952 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]1([CH:37]=O)[CH2:36][CH2:35][CH2:34][CH2:33]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].ClCCl>ClCCCl>[CH3:27][O:26][C:24](=[O:25])[C:23]1[CH:28]=[C:19]([N:18]([CH2:17][C:16]2[CH:15]=[CH:14][C:13]([C:12]#[C:11][C:8]3[CH:7]=[CH:6][C:5]([CH2:1][CH2:2][CH2:3][CH3:4])=[CH:10][CH:9]=3)=[CH:31][CH:30]=2)[CH2:37][CH:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)[CH:20]=[CH:21][C:22]=1[F:29]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 70106CyclopentanecarbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 11452740Methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-fluorobenzoate

Product 1

HCID 575545035-{[4-(4-Butyl-phenylethynyl)-benzyl]-cyclopentylmethylamino}-2-fluoro-benzoic acid methyl esterYield 61.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

A solution of methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-fluorobenzoate (800 mg, 1.93 mmol) in DCE (16 mL) was treated with cyclopentanecarboxaldehyde (Aldrich, 283 mg, 2.89 mmol) then with sodium triacetoxyborohydride (1.22 g, 5.78 mmol). The resulting mixture was stirred at 70° C. for 2 h. The reaction mixture was allowed to cool down, dichloromethane (40 mL) was added and the organic layer was washed twice with water and with brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silicagel afforded the title compound as a colorless oil (590 mg, 60%). HPLC, Rt: 6.47 min (purity: 97.1%), LC/MS, M+(ESI): 498.1. 1H NMR (CDCl3) δ: 7.42 (m, 4H), 7.22 (m, 1M), 7.14 (m, 4H), 6.92 (m, 1H), 6.75 (m, 1H), 4.55 (s, 2H), 3.89 (s, 3H), 3.33 (d, 2H), 2.60 (t, J=7.7 Hz, 2H), 2.29 (m, 1H), 1.65 (m, 2H), 1.70-1.46 (m, 6H), 1.42-1.15 (m, 6H), 0.91 (t, J=7.3 Hz, 3H).

Workup

  1. temperatureto cool down
  2. washthe organic layer was washed twice with water and with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography on silicagel

Sources & evidence

ORD record
ord-300318418091483a8590a2458ff1f91b
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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