Dimethylamine → 6-Dimethylamino-2-naphthaldehyde

HRID 400338Notes

Reaction equation

HRID 400338 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH3:13])[CH:8]=2)[CH:3]=1.[CH2:14]([Li])[CH2:15][CH2:16][CH3:17].[CH3:19][NH:20][CH3:21].[CH3:22][O:23]C1C=[C:26]2[C:31](=CC=1)[C:30]([CH:34]=[O:35])=[CH:29][CH:28]=[CH:27]2.P([O-])([O-])([O-])=O>CCOCC.CN(C)P(N(C)C)(N(C)C)=O.C1C=CC=CC=1.CN(C)C=O>[CH3:13][O:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[CH:3]=[C:2]([CH:22]=[O:23])[CH:11]=[CH:10]2.[CH3:19][N:20]([CH3:21])[C:15]1[CH:16]=[C:17]2[C:28](=[CH:27][CH:14]=1)[CH:29]=[C:30]([CH:34]=[O:35])[CH:31]=[CH:26]2

Participants

11

Reactant 5

HCID 674DimethylamineHCID 1061PhosphateHCID 787862-Bromo-6-methoxynaphthaleneHCID 128430406-Methoxynaphthalene-1-carbaldehydeHCID 178418339Butyllithium2×

Product 2

HCID 769916-Methoxy-2-naphthaldehydeHCID 251953866-Dimethylamino-2-naphthaldehydeYield 84%

Reagents, catalysts & solvents 4

HCID 241BenzeneSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

6-Methoxy-2-naphthaldehyde is prepared by successive treatment of 2-bromo-6-methoxynaphthalene in solution in dry ether with n-butyllithium and then dimethylformamide. (Literature: J. Med. Chem. 1998, 1308-1312). 6-Dimethylamino-2-naphthaldehyde is prepared according to the described procedure (Barbas et al., Proc. Natl. Acad. Sci. USA 1998, 95, 15351) as follows: gaseous dimethylamine is introduced into a mixture of 2.4 ml of dry benzene and 2.4 ml of hexamethylphosphoramide (HMPA) until 750 mg (16.7 mmol) is dissolved. At 0° C. and under inert atmosphere, n-butyllithium (1.6 M in hexane, 16.7 mmol) is added, then after 15 minutes, 6-methoxy-naphthaldehyde (390 mg, 2.09 mmol) is added. Stirring is continued for 14 hours at 20° C., then it is poured into aqueous phosphate buffer, pH 7.4, and it is extracted with ether. Purification by chromatography provides 6-dimethylamino-2-naphthaldehyde (350 mg, 84%).

Workup

  1. custom6-Dimethylamino-2-naphthaldehyde is prepared
  2. dissolutionis dissolved
  3. waitis continued for 14 hours at 20° C.
  4. extractionis extracted with ether
  5. customPurification by chromatography

Sources & evidence

ORD record
ord-f0477b0764b64b7ab819b69a1391aa26
Source dataset
uspto-grants-2014_06
Patent number
US08741593B2

Reaction notes

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