Tetrahydrofuran → HCID 69673663, compound

HRID 2276352Notes

Reaction equation

HRID 2276352 reaction equation
[C:1]1([C:7]2[O:8][C:9](=[O:21])[C:10]3[CH:20]=[C:19]4[C:14]([CH2:15][CH2:16][CH2:17][CH2:18]4)=[CH:13][C:11]=3[N:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:22]1([CH3:30])[CH:27]=[CH:26][C:25]([Mg]Br)=[CH:24][CH:23]=1.O1CCCC1>ClCCl>[CH3:30][C:22]1[CH:27]=[CH:26][C:25]([C:9]([C:10]2[C:11]([NH:12][C:7](=[O:8])[C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:13][C:14]3[CH2:15][CH2:16][CH2:17][CH2:18][C:19]=3[CH:20]=2)=[O:21])=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 69673097HCID 69673097, compoundHCID 178418370HCID 178418370, compound2×

Product 1

HCID 69673663HCID 69673663, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-[3-(4-Methyl-benzoyl)-5,6,7,8-tetrahydro-naphthalen-2-yl]-benzamide was prepared by a modification of the route described in Okabe, M. and Sun, R. C.; Tetrahedron 1995, 51(7), 1861-1866). To a 100 mL flask containing a solution 2-phenyl-6,7,8,9-tetrahydro-naphtho[2,3-d][1,3]oxazin-4-one (220 mg, 0.793 mmol) in dichloromethane (20 mL) under nitrogen and cooled to −78 C was added dropwise by syringe p-tolylmagnesium bromide solution in tetrahydrofuran (1.0 M, 0.87 mL, 0.87 mmol) and the yellow solution was allowed to warm to room temperature overnight with stirring. Reaction had not proceeded to completion and was re-cooled to −78 C and added more p-tolylmagnesium bromide solution (0.30 mL, 0.38 eq) and transferred the reaction to an acetonitrile-CO2 bath (−42 C) and stirred for 1 hour. Quenched by addition of saturated ammonium chloride solution (2 mL) and allowed to warm to ambient temperature. Diluted further with water (10 mL) and the organic fraction was removed using a hydrophobic frit, evaporated onto silica gel, and chromatographed using ISCO Companion with a Redisep silica gel 40 g cartridge and a gradient of heptane and ethyl acetate (0% to 20%). Evaporation gave N-[3-(4-methyl-benzoyl)-5,6,7,8-tetrahydro-naphthalen-2-yl]-benzamide as a pale yellow solid 191.4 mg (65.3% Yield). LCMS (5 min acidic) 3.52 min 100% pure by ELSD and UV ES+ 370. HNMR (CDCl3) >95% pure 11.69 (s, 1H), 8.08-8.06 (m, 2H), 7.65-7.63 (m, 2H), 7.55-7.48 (m, 3H), 7.33-7.29 (m, 3H), 2.92-2.89 (m, 2H), 2.71-2.68 (m, 2H), 2.46 (s, 3H), 1.87-1.79 (m, 4H).

Workup

  1. customN-[3-(4-Methyl-benzoyl)-5,6,7,8-tetrahydro-naphthalen-2-yl]-benzamide was prepared by a modification of the route
  2. temperaturecooled to −78 C
  3. customReaction
  4. temperaturewas re-cooled to −78 C
  5. customthe reaction to an acetonitrile-CO2 bath (−42 C)
  6. stirringstirred for 1 hour
  7. customQuenched by addition of saturated ammonium chloride solution (2 mL)
  8. temperatureto warm to ambient temperature
  9. additionDiluted further with water (10 mL)
  10. customthe organic fraction was removed
  11. customevaporated onto silica gel
  12. customchromatographed
  13. customEvaporation

Sources & evidence

ORD record
ord-30264da161ee477088c983a132b589cc
Source dataset
uspto-grants-2015_09
Patent number
US09132129B2

Reaction notes

Loading…