4-(3-Bromo-5-chlorophenyl)morpholine → HCID 59631266, compound

HRID 1431760Notes

Reaction equation

HRID 1431760 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[F:15][C:16]1[CH:25]=[C:24]2[C:19]([C:20]([CH:33]=[O:34])=[C:21]([CH3:32])[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)=[N:23]2)=[CH:18][CH:17]=1>C1COCC1>[Cl:8][C:6]1[CH:7]=[C:2]([CH:33]([C:20]2[C:19]3[C:24](=[CH:25][C:16]([F:15])=[CH:17][CH:18]=3)[N:23]=[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[C:21]=2[CH3:32])[OH:34])[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=1

Participants

4

Reactant 2

HCID 532170884-(3-Bromo-5-chlorophenyl)morpholineHCID 59631569HCID 59631569, compound

Product 1

HCID 59631266HCID 59631266, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

An oven-dried conical flask was charged with 4-(3-bromo-5-chlorophenyl)-morpholine (0.384 g, 1.390 mmol) and 1.0 mL THF. While this solution was stirring at −78° C. under nitrogen, 2.5M butyllithium hexanes (0.556 mL, 1.390 mmol) was added via syringe. This solution was stirred at −78° C. for 30 minutes. After this time a solution of 7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline-4-carbaldehyde (0.074 g, 0.278 mmol) in 2.0 mL THF was added, and the reaction continued at −78° C. for 45 minutes. Upon completion, the reaction was quenched with satd aqueous ammonium chloride and concd. The resulting material was partitioned between EtOAc and water, and the organic phase was dried over magnesium sulfate and concd. The afforded crude product was purified by column chromatography (silica; 0-50% EtOAc in hexanes) to yield (3-chloro-5-(4-morpholinyl)phenyl)(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)methanol as a white amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.70 (1H, d), 8.35 (1H, m), 8.01 (1H, t), 7.83 (1H, s), 7.71 (1H, d), 7.51 (1H, m), 7.42 (1H, m), 6.97 (1H, s), 6.83 (1H, s), 6.64 (1H, d, J=4.5 Hz), 6.55 (1H, d), 6.51 (1H, s), 3.69 (4H, t, J=4.8 Hz), 3.08 (4H, d, J=3.9 Hz), 2.46 (3H, s). Mass Spectrum (ESI) m/e=464.0 (M+1).

Workup

  1. stirringThis solution was stirred at −78° C. for 30 minutes
  2. customUpon completion, the reaction was quenched with satd aqueous ammonium chloride and concd
  3. customThe resulting material was partitioned between EtOAc and water
  4. dry with materialthe organic phase was dried over magnesium sulfate and concd
  5. customThe afforded crude product
  6. customwas purified by column chromatography (silica; 0-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ae3f3798d0184943b8a40231a990dbe7
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

Loading…