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Tetrahydrofuran → 6-chloro-N-cyclohexyl-2-[2-(4-fluorophenyl)ethoxy]nicotinamide

HRID 2424906
Notes
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Reaction equation

HRID 2424906 reaction equation
Cl[C:2]1[C:7]([C:8]([NH:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[O:9])=[CH:6][CH:5]=[C:4]([Cl:17])[N:3]=1.[F:18][C:19]1[CH:27]=[CH:26][C:22]([CH2:23][CH2:24][OH:25])=[CH:21][CH:20]=1.C1COCC1>O1CCOCC1>[Cl:17][C:4]1[CH:5]=[CH:6][C:7]([C:8]([NH:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[O:9])=[C:2]([O:25][CH2:24][CH2:23][C:22]2[CH:26]=[CH:27][C:19]([F:18])=[CH:20][CH:21]=2)[N:3]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 820684-Fluorophenethyl AlcoholHCID 527624932,6-dichloro-N-cyclohexylnicotinamide2×

Product 1

HCID 598306816-chloro-N-cyclohexyl-2-[2-(4-fluorophenyl)ethoxy]nicotinamideYield 40.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

2,6-dichloro-N-cyclohexylnicotinamide (Intermediate 1, 273 mg, 1 mmol) was stirred in 1,4-dioxane (4 ml). To this solution was added 4-fluorophenethyl alcohol (154 mg, 1.1 mmol) followed by bis-sodium hexamethyldisilylamide 1.0M in THF (1.1 ml, 1.1 mmol). The tube was sealed and subjected to microwave heating 150° C. (Biotage Initiator 300 W) for 2 hours. The solvent was evaporated and the residue was diluted with water (15 ml) and extracted with dichloromethane (2×20 ml). The combined extract was washed with brine (20 ml) dried over MgSO4, filtered and evaporated. The crude product was purified on SiO2 (40 g) eluting with ethyl acetate/isohexane 0-40% and gave 6-chloro-N-cyclohexyl-2-[2-(4-fluorophenyl)ethoxy]nicotinamide (153 mg, 40%) as a white solid

Workup

  1. customThe tube was sealed
  2. customThe solvent was evaporated
  3. additionthe residue was diluted with water (15 ml)
  4. extractionextracted with dichloromethane (2×20 ml)
  5. extractionThe combined extract
  6. washwas washed with brine (20 ml)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified on SiO2 (40 g)
  11. washeluting with ethyl acetate/isohexane 0-40%

Sources & evidence

ORD record
ord-ef46e12fb5634b5387d541d04851c4e1
Source dataset
uspto-grants-2011_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07964618B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes