Borane;tetrahydrofuran → Ethyl 3-(1-(aminomethyl)cyclopentyl)-5-(hydroxymethyl)benzoate

HRID 899461Notes

Reaction equation

HRID 899461 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([C:15]2([C:20]#[N:21])[CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:14]=1)[C:9](O)=[O:10])=[O:5])[CH3:2].B.O1CCCC1>C1COCC1>[NH2:21][CH2:20][C:15]1([C:13]2[CH:14]=[C:6]([CH:7]=[C:8]([CH2:9][OH:10])[CH:12]=2)[C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:19][CH2:18][CH2:17][CH2:16]1.[C:20]([C:15]1([C:13]2[CH:14]=[C:6]([CH:7]=[C:8]([CH2:9][OH:10])[CH:12]=2)[C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:19][CH2:18][CH2:17][CH2:16]1)#[N:21]

Participants

5

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 673184623-(Ethoxycarbonyl)-5-(1-cyanocyclopentyl)benzoic acid

Product 2

HCID 67319676Ethyl 3-(1-(aminomethyl)cyclopentyl)-5-(hydroxymethyl)benzoateHCID 67319946Ethyl 3-(1-cyanocyclopentyl)-5-(hydroxymethyl)benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-(ethoxycarbonyl)-5-(1-cyanocyclopentyl)benzoic acid (0.4 g, 1.4 mmol) in 14 mL THF, cooled to 0° C., was added borane-tetrahydrofuran complex (1M in THF, 5.6 mL, 5.6 mmol) dropwise. The reaction was stirred at 0° C. for 1.5 h and then at rt for 3.5 h. The mixture was quenched with MeOH, concentrated, diluted with EtOAc and washed with water and brine. Drying and solvent evaporation gave ethyl 3-(1-(aminomethyl)cyclopentyl)-5-(hydroxymethyl)benzoate and ethyl 3-(1-cyanocyclopentyl)-5-(hydroxymethyl)benzoate. The crude mixture was dissolved in 6.6 mL CH2Cl2, cooled to 0° C. and treated with carbon tetrabromide (0.56 g, 1.7 mmol). A solution of triphenylphosphine (0.42 g, 1.6 mmol) in 6.6 mL CH2Cl2 was added and the reaction was stirred at 0° C. for 1 h. Concentration and flash chromatography (silica gel, 0-20% EtOAc/hexanes) gave ethyl 3-(bromomethyl)-5-(1-cyanocyclopentyl)benzoate. 1H NMR (400 MHz, CDCl3) δ 8.02 (t, J=1.9 Hz, 2H), 7.70 (t, J=1.7 Hz, 1H), 4.52 (s, 2H), 4.41 (q, J=7.1 Hz, 2H), 2.53 (m, 2H), 2.12-1.97 (m, 6H), 1.41 (t, J=7.1 Hz, 3H).

Workup

  1. waitat rt for 3.5 h
  2. customThe mixture was quenched with MeOH
  3. concentrationconcentrated
  4. additiondiluted with EtOAc
  5. washwashed with water and brine
  6. customDrying
  7. customsolvent evaporation

Sources & evidence

ORD record
ord-fca1b8d0b0644f78bedef90755752ef7
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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