Hexane → 4-Bromo-4'-morpholinobenzophenone

HRID 1392989Notes

Reaction equation

HRID 1392989 reaction equation
C([Li])CCC.CCCCCC.Br[C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[CH:15][CH:14]=1.[Br:25][C:26]1[CH:37]=[CH:36][C:29]([C:30](N(OC)C)=[O:31])=[CH:28][CH:27]=1>O1CCCC1>[Br:25][C:26]1[CH:37]=[CH:36][C:29]([C:30]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[CH:15][CH:14]=2)=[O:31])=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 109992524-Bromo-N-methoxy-N-methylbenzamideHCID 116228514-(4-Bromophenyl)morpholineHCID 178418339Butyllithium

Product 1

HCID 692000794-Bromo-4'-morpholinobenzophenoneYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of n-butyllithium in hexane (1.6 M, 0.49 mL, 0.79 mmol) was added dropwise to a solution of 4-(4-bromophenyl)morpholine (191 mg, 0.79 mmol; described in: Jones, D. H. J. Chem. Soc. (C), 1971, 132-137 ) in tetrahydrofuran (5 mL) under nitrogen at −78° C. After 10 minutes, a pre-cooled solution (−78° C.) of 4-bromo-N-methoxy-N-methylbenzamide (212 mg, 0.87 mmol; described in: Turnbull, K. Tet. Lett. 1998 39(12), 1509-12) in tetrahydrofuran (3 mL) was added via a double-tipped needle. The mixture was stirred at −78° C. for 5 min. The cooling bath was removed and the mixture was allowed to reach ambient temperature under 30 min. The solvent was removed in vacuo, and the residue was partitioned between ethyl acetate and water. The phases were separated and the organic layer was washed with brine, dried (MgSO4) and the solvent was removed in vacuo. The crude product was purified by column chromatography on silica gel using heptane/ethyl acetate, 70:30, as the eluent affording 86 mg (32% yield) of the title compound as colorless crystals: mp 177.8-179.2° C.; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J=9.0 Hz, 2 H), 7.61 (s, 4 H), 6.89 (d, J=9.0 Hz, 2 H), 3.89-3.85 (m, 4 H), 3.35-3.32 13C NMR(400 MHz, CDCl3) δ 194.5, 154.6, 137.8, 132.8, 131.8, 131.6, 127.7, 126.8, 113.6, 67.0, 47.9; MS (TSP) m/z 346 (M+1).

Workup

  1. customThe cooling bath was removed
  2. waitto reach ambient temperature under 30 min
  3. customThe solvent was removed in vacuo
  4. customthe residue was partitioned between ethyl acetate and water
  5. customThe phases were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent was removed in vacuo
  9. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-fc806634f08b4975aacf3bc466ad1308
Source dataset
uspto-grants-2008_03
Patent number
US07345050B2

Reaction notes

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