Formamide → 2-(2-Chloro-7-dimethylaminomethyl-naphthalen-1-yl)-acetamide

HRID 1992625Notes

Reaction equation

C([O:3][C:4](=O)[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH2:16][N:17]([CH3:19])[CH3:18])[CH:14]=2)[CH:9]=[CH:8][C:7]=1[Cl:20])C.C([NH2:24])=O.C[O-].[Na+]>CN(C=O)C.CO>[Cl:20][C:7]1[CH:8]=[CH:9][C:10]2[C:15](=[CH:14][C:13]([CH2:16][N:17]([CH3:19])[CH3:18])=[CH:12][CH:11]=2)[C:6]=1[CH2:5][C:4]([NH2:24])=[O:3]

Participants

Conditions

Temperature: 105 °C

Procedure

(2-Chloro-7-dimethylaminomethyl-naphthalen-1-yl)-acetic acid ethyl ester (2.70 g, 8.82 mmol) and formamide (1.17 ml, 29.57 mmol) are dissolved under an atmosphere of argon in dry DMF (25 ml). The solution is heated to 105° C., and NaOMe (1.64 ml of a 5.4 M solution in MeOH, 8.82 mmol) is added dropwise during 10 minutes. After 1 hour at 105° C., TLC analysis indicates complete consumption of starting material. The reaction mixture is cooled to RT, diluted with water, and adjusted to a pH of 6-7 by the addition of 1 M NaHSO4 solution. The mixture is concentrated and purified by FCC (CH2Cl2/EtOH/NH3 conc. 90:9:1) to yield the title compound. 1H NMR (d6-DMSO, 400 MHz): δ 2.01 (s, 6H), 3.48 (s, 3H), 4.02 (s, 3H), 6.9-7.0 (br, 1H), 7.41-7.47 (m, 2H); 7.47-7.85 (br, 1H), 7.75-7.88 (m, 2H), 7.80 (d, J=12.1 Hz, 1H). ES+−MS: 277.3, 279.2 [M+H]+.

Workup

customconsumption of starting material
temperatureThe reaction mixture is cooled to RT
additiondiluted with water
additionadjusted to a pH of 6-7 by the addition of 1 M NaHSO4 solution
concentrationThe mixture is concentrated
custompurified by FCC (CH2Cl2/EtOH/NH3 conc. 90:9:1)

Sources & evidence

ORD record: ord-0b0f9666bf6f47888d71cf591ed5ef69
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07648989B2

Reaction notes

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