Toluene → HCID 58381033, compound

HRID 45205Notes

Reaction equation

HRID 45205 reaction equation
[NH2:1][C:2]([CH:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]1)([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:3].[C:17]1([CH3:23])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[H-].[Na+].C(ON1C2[C:38](=[CH:39][C:40](F)=[C:41]([Cl:44])[CH:42]=2)[CH:37]=CC1)C1C=CC=CC=1.[CH3:46][C:47]([N:49]([CH3:51])C)=[O:48]>ClCCl.C(O)(C)C.O>[CH2:23]([O:48][C:47]1[C:46]2[C:38](=[CH:39][C:40]([O:16][CH:13]3[CH2:14][CH2:15][CH:10]([C:2]([NH2:1])([C:4]4[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=4)[CH3:3])[CH2:11][CH2:12]3)=[C:41]([Cl:44])[CH:42]=2)[CH:37]=[CH:51][N:49]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

8

Reactant 5

HCID 1140TolueneHCID 24758Sodium hydrideHCID 31374Dimethylacetamide3×HCID 58380998HCID 58380998, compoundHCID 670756391-Benzyloxy-7-chloro-6-fluoroquinoline

Product 1

HCID 58381033HCID 58381033, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21966342Isopropanol methylene chlorideSolvent

Procedure

4-(1-Amino-1-phenyl-ethyl)-cyclohexanol (30, 404 mg, 1.6 mmol) was evaporated twice to dryness from toluene. The residue was dissolved in dimethylacetamide (3 mL) and the solution added dropwise to a suspension of sodium hydride (114 mg, 4.1 mmol, 60% in mineral oil) in dimethyl acetamide (8 mL) under argon. After stirring for 1 hour, a solution of 1-benzyloxy-7-chloro-6-fluoroquinoline (38, 0.31 g, 1.09 mmol) in dimethylacetamide (6 mL) was added dropwise and the mixture stirred overnight. Then mixture was then heated and stirred at 60° C. for 1 hour before cooling and addition of water (30 mL) to quench the reaction. The product was isolated by extraction with dichloromethane/isopropanol (3:1) and evaporation of the organic phase under reduced pressure. Purification by column chromatography (silica gel, 2% methanol in dichloromethane) gave the desired product (67 mg) as a colourless solid. Rt=4.3 min (Method 3). Detected mass: 487.3 (M+H+).

Workup

  1. stirringthe mixture stirred overnight
  2. temperatureThen mixture was then heated
  3. stirringstirred at 60° C. for 1 hour
  4. temperaturebefore cooling
  5. customto quench
  6. customthe reaction
  7. customPurification by column chromatography (silica gel, 2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-7475fb93a72f402c9e885fae09c01af3
Source dataset
uspto-grants-2013_09
Patent number
US08541449B2

Reaction notes

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