Acetic Acid → (2-Chloro-6-dimethylaminomethyl-naphthalen-1-yl)-acetic acid ethyl ester

HRID 639198Notes

Reaction equation

HRID 639198 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][C:15]([CH:19]=O)=[CH:16][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][C:15]([CH2:19][N:2]([CH3:3])[CH3:1])=[CH:16][CH:17]=2)[CH:12]=[CH:11][C:10]=1[Cl:21])[CH3:5]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 674DimethylamineHCID 5003444Sodium cyanoborohydrideHCID 86623397(2-Chloro-6-formyl-naphthalen-1-yl)-acetic acid ethyl ester

Product 1

HCID 68704219(2-Chloro-6-dimethylaminomethyl-naphthalen-1-yl)-acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dimethylamine (5.6 M solution in EtOH, 0.28 ml, 1.53 mmol) is added under an atmosphere of argon to a solution of (2-chloro-6-formyl-naphthalen-1-yl)-acetic acid ethyl ester (284 mg, 1.02 mmol) in THF (10 ml). The mixture is stirred at RT for 18 h, before a solution of sodium cyanoborohydride (78 mg, 1.23 mmol) in MeOH (2 ml) and glacial acetic acid (0.29 ml, 5.13 mmol) are added. After stirring at RT for 1 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 (CH2Cl2/EtOH/NH3 190:9:1) affords the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.26 (t, J=9 Hz, 3H), 2.30 (s, 6H), 3.59 (s, 2H), 4.18 (q, J=9 Hz, 2H), 4.30 (s, 2H), 7.49 (d, J=10 Hz, 1H), 7.54-7.58 (m, 1H), 7.69-7.76 (m, 2H), 7.91 (d, J=10 Hz, 1H). ES+-MS: 306.4, 308.3 [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 (CH2Cl2/EtOH/NH3 190:9:1)

Sources & evidence

ORD record
ord-af7f360f697f4d37b2b92b081b96c115
Source dataset
uspto-grants-2010_04
Patent number
US07691861B2

Reaction notes

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