Acetic Acid → 3-Chloro-8-dimethylaminomethyl-naphthalene-2-carboxylic acid ethyl ester

HRID 1968755Notes

Reaction equation

HRID 1968755 reaction equation
[CH3:1][NH:2][CH3:3].[CH2:4]([O:6][C:7]([C:9]1[C:18]([Cl:19])=[CH:17][C:16]2[C:11](=[C:12]([CH:20]=O)[CH:13]=[CH:14][CH:15]=2)[CH:10]=1)=[O:8])[CH3:5].C([BH3-])#N.[Na+].C(O)(=O)C>C1COCC1.CO>[CH2:4]([O:6][C:7]([C:9]1[C:18]([Cl:19])=[CH:17][C:16]2[C:11](=[C:12]([CH2:20][N:2]([CH3:3])[CH3:1])[CH:13]=[CH:14][CH:15]=2)[CH:10]=1)=[O:8])[CH3:5]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 674DimethylamineHCID 5003444Sodium cyanoborohydrideHCID 71424625Ethyl 3-chloro-8-formylnaphthalene-2-carboxylate

Product 1

HCID 668827963-Chloro-8-dimethylaminomethyl-naphthalene-2-carboxylic acid ethyl esterYield 34.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of dimethylamine (5.6 M in EtOH, 0.36 ml, 2.0 mmol, 1.5 equiv) was added to a solution of 3-chloro-8-formyl-naphthalene-2-carboxylic acid ethyl ester (350 mg, 1.33 mmol) in THF (6.5 ml). After stirring at room temperature for 16 hours, a solution of sodium cyanoborohydride (101 mg, 1.6 mmol, 1.2 equiv) in MeOH (3.0 ml) and acetic acid (0.38 ml, 6.7 mmol, 5.0 equiv) were added, and the reaction mixture was stirred at room temperature for 3 hours. After dilution with water (75 ml), the mixture was extracted with CH2Cl2 (total of 400 ml). The combined organic layers were washed with concentrated aqueous NaHCO3 solution, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via flash chromatography (gradient of hexane/EtOAc 100:0 to 1:2) to afford the title compound (133 mg, 34%) as a mixture of regioisomers, which could be separated for analytical purposes. 3-Chloro-8-dimethylaminomethyl-naphthalene-2-carboxylic acid ethyl ester 1H NMR (400 MHz, CDCl3): δ=8.72 (s, 1H), 8.08 (s, 1H), 7.87 (d, J=7.7 Hz, 1H), 7.61-7.55 (m, 2H), 4.42 (q, J=7.1 Hz, 2H), 3.97 (br s, 2H), 2.33 (s, 6H), 1.40 (t, J=7.1 Hz, 3H). MS (ES+): 292 (M+H)+. 3-Chloro-5-dimethylaminomethyl-naphthalene-2-carboxylic acid ethyl ester: 1H NMR (400 MHz, CDCl3): δ=8.39 (s, 1H), 8.35 (s, 1H), 7.94 (d, J=7.8 Hz, 1H), 7.57-7.50 (m, 2H), 4.41 (q, J=7.1 Hz, 2H), 3.81 (s, 2H), 2.24 (s, 6H), 1.40 (t, J=7.1 Hz, 3H). MS (ES+): 292 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 3 hours
  2. extractionAfter dilution with water (75 ml), the mixture was extracted with CH2Cl2 (total of 400 ml)
  3. washThe combined organic layers were washed with concentrated aqueous NaHCO3 solution
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via flash chromatography (gradient of hexane/EtOAc 100:0 to 1:2)

Sources & evidence

ORD record
ord-4148cb7f3c9c45e09cc98ba9f34f54ca
Source dataset
uspto-grants-2013_04
Patent number
US08426440B2

Reaction notes

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