Chloromethyl Methyl Ether → 8-Chloro-7-methoxymethylquinoline

HRID 1920681Notes

Reaction equation

HRID 1920681 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[C:10](O)=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16](C)[CH:15]=[CH:14]2.[CH3:21][O:22][CH2:23]Cl>C1COCC1.CCOC(C)=O>[Cl:8][C:9]1[C:10]([CH2:21][O:22][CH3:23])=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2

Participants

6

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 8471TriethylamineHCID 1358589748-Chloro-2-methylquinolin-7-ol

Product 1

HCID 674918338-Chloro-7-methoxymethylquinolineYield 72%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Referring to FIG. 20, triethylamine (1.879 mL, 13.49 mmol) was added to a solution of 5c (0.2612 g, 1.349 mmol) in THF (20 mL) under a nitrogen atmosphere. Chloromethyl methyl ether (0.241 mL, 3.17 mmol) was added to the mixture dropwise. After stirring for 2 h, the solution was diluted with EtOAc and washed successively with water (×2) and brine. The organic layer was dried over MgSO4, filtered, and evaporated. The resulting residue was purified by flash chromatography (3:7 EtOAc/hexane) to afford 8c (0.2298 g, 0.9668 mmol, 72%) as a yellow solid (mp 78-79° C.): 1H NMR (CDCl3) δ 8.01 (1H, d, J=8.8 Hz), 7.67 (1H, d, J=8.8 Hz), 7.47 (1H, d, J=9.2 Hz), 7.26 (1H, d, J=8.8 Hz), 5.40 (2H, s), 3.58 (3H, s), 2.82 (3H, s); 13C NMR (CDCl3) δ 160.9, 153.8, 145.4, 136.6, 126.9, 123.5, 121.4, 116.7, 105.0, 95.7, 56.8, 26.0; FTIR (neat) 2919, 1611, 1508, 1259, 1011, 833, 783 cm−1; MS (ESI) m/z calculated for (C12H12ClNO2+H)+ 238 (35Cl) and 240 (37Cl), found 238 (35Cl) and 240 (37Cl); HRMS (ESI) m/z calculated for (C12H12ClNO2+H)+ 238.0635 (35Cl) and 240.0605 (37Cl), found 238.0623 (35Cl) and 240.0593 (37Cl).

Workup

  1. washwashed successively with water (×2) and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe resulting residue was purified by flash chromatography (3:7 EtOAc/hexane)

Sources & evidence

ORD record
ord-f9f88e6397054d10981de8f07de173f8
Source dataset
uspto-grants-2012_05
Patent number
US08173620B2

Reaction notes

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