Acetic Acid → (2-Chloro-7-dimethylaminomethyl-naphthalen-1-yl)-acetic acid ethyl ester

HRID 1992626Notes

Reaction equation

HRID 1992626 reaction equation
[CH3:1][NH:2][CH3:3].[CH2:4]([O:6][C:7](=[O:22])[CH2:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH:19]=O)[CH:17]=2)[CH:12]=[CH:11][C:10]=1[Cl:21])[CH3:5].C([BH3-])#N.[Na+].C(O)(=O)C>C1COCC1.CO>[CH2:4]([O:6][C:7](=[O:22])[CH2:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:19][N:2]([CH3:3])[CH3:1])[CH:17]=2)[CH:12]=[CH:11][C:10]=1[Cl:21])[CH3:5]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 674DimethylamineHCID 5003444Sodium cyanoborohydrideHCID 86061793(2-Chloro-7-formyl-naphthalen-1-yl)-acetic acid ethyl ester

Product 1

HCID 66868949(2-Chloro-7-dimethylaminomethyl-naphthalen-1-yl)-acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dimethylamine (5.6 M solution in EtOH, 4.2 ml, 23.20 mmol) is added under an atmosphere of argon to a solution of (2-Chloro-7-formyl-naphthalen-1-yl)-acetic acid ethyl ester (4.28 g, 15.46 mmol) in THF (80 ml). The mixture is stirred at RT for 18 h, before a solution of sodium cyanoborohydride (1.16 g, 18.56 mmol) in MeOH (20 ml) and glacial acetic acid (4.4 ml, 77.33 mmol) are added. After stirring at RT for 2 h, TLC analysis indicates complete consumption of starting material. The reaction mixture is diluted with water and adjusted to pH 8-9 by the addition of conc. aq. NaHCO3 solution. Extraction with EtOAc, washing with brine, drying over Na2SO4 and removal of solvent yields the crude reaction product. Purification by FCC (EtOAc, then EtOAc/MeOH 4:1) affords the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.26 (t, J=8.8 Hz, 3H), 2.28 (s, 6H), 3.62 (s, 3H), 4.18 (q, J=8.8 Hz, 2H), 4.32 (s, 3H), 7.48 (d, J=9.9 Hz, 1H), 7.52 (d, J=9.9 Hz, 1H), 7.73 (d, J=9.9 Hz, 1H), 7.80-7.84 (m, 2H). ES+−MS: 306.3, 308.2. [M+H]+.

Workup

  1. additionare added
  2. customconsumption of starting material
  3. additionThe reaction mixture is diluted with water
  4. additionadjusted to pH 8-9 by the addition of conc. aq. NaHCO3 solution
  5. extractionExtraction with EtOAc
  6. washwashing with brine
  7. dry with materialdrying over Na2SO4 and removal of solvent
  8. customyields the crude
  9. customreaction product
  10. customPurification by FCC (EtOAc

Sources & evidence

ORD record
ord-ce1e3db556a04ee084420e19cb0c8e09
Source dataset
uspto-grants-2010_01
Patent number
US07648989B2

Reaction notes

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