Tributylamine → [2-(2,5-Dichloro-phenoxy)-5-fluoro-phenyl]-(2-methyl-3,4-dihydro-2H-quinolin-1-yl)-methanone

HRID 1877381Notes

Reaction equation

HRID 1877381 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:6]=1[C:7]([OH:9])=O.[CH3:20][CH:21]1[CH2:30][CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[NH:22]1.C(N(CCCC)CCCC)CCC.[I-].ClC1C=CC=C[N+]=1C>ClCCl>[Cl:1][C:2]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:6]=1[C:7]([N:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:29][CH2:30][CH:21]1[CH3:20])=[O:9]

Participants

6

Reactant 4

HCID 7622TributylamineHCID 962892-Methyl-1,2,3,4-tetrahydroquinolineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 43313245HCID 43313245, compound

Product 1

HCID 46195126[2-(2,5-Dichloro-phenoxy)-5-fluoro-phenyl]-(2-methyl-3,4-dihydro-2H-quinolin-1-yl)-methanoneYield 15.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 2-(2,5-dichloro-phenoxy)-5-fluoro-benzoic acid (36.1 mg, 0.12 mmol, 1.0 equiv; Example 113, Step 1) in dichloromethane (1 mL) was added 2-methyl-1,2,3,4-tetrahydro-quinoline (21.2 mg, 0.14 mmol, 1.2 equiv; [CAS RN 1780-19-4]), tri-n-butylamine (111.2 mg, 143 μL, 0.60 mmol, 5.0 equiv; [CAS RN 102-82-9]) and 2-chloro-1-methylpyridinium iodide (36.8 mg, 0.14 mmol, 1.2 equiv; [CAS RN 14338-32-0]). The reaction mixture was heated to 40° C. over night. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μM, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 7.8 mg (15%) of the title compound. MS (ISP): 430.1 [M+H]+.

Workup

  1. customRemoval of the solvent mixture
  2. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μM, 19×50 mm column
  3. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  4. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-0a149e800226474ba9ee35b6a36e830a
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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