Sodium Carbonate → 1-[6-[3-(4-Morpholinyl)-5-nitrophenyl]-2-pyridinyl]cyclobutanol

HRID 2207352Notes

Reaction equation

HRID 2207352 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Br[C:8]1[N:13]=[C:12]([C:14]2([OH:18])[CH2:17][CH2:16][CH2:15]2)[CH:11]=[CH:10][CH:9]=1.[N+:19]([C:22]1[CH:23]=[C:24]([N:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)[CH:25]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:27]=1)([O-:21])=[O:20]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[N:37]1([C:24]2[CH:25]=[C:26]([C:8]3[N:13]=[C:12]([C:14]4([OH:18])[CH2:17][CH2:16][CH2:15]4)[CH:11]=[CH:10][CH:9]=3)[CH:27]=[C:22]([N+:19]([O-:21])=[O:20])[CH:23]=2)[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 589324181-(6-Bromopyridin-2-yl)cyclobutanolHCID 672568704-(3-Nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)morpholine

Product 1

HCID 1180930551-[6-[3-(4-Morpholinyl)-5-nitrophenyl]-2-pyridinyl]cyclobutanol

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

Pd(dppf)Cl2-dichloromethane adduct (40.8 mg, 0.05 mmol) and sodium carbonate (2 N, 1.5 mL, 3.0 mmol) were added to 1-(6-bromopyridin-2-yl)cyclobutanol (228 mg, 1.0 mmol) and 4-[3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]morpholine (0.2 N in DMF, 5.0 mL, 1.0 mmol) and the reaction mixture was purged and flushed with N2(g) (3×). The reaction mixture was heated to 100° C. for 4 hours, then cooled to room temperature, diluted with water, extracted with diethyl ether, washed with brine, dried over sodium sulfate, filtered an concentrated under reduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate:hexanes) to afford 1-{6-[3-(morpholin-4-yl)-5-nitrophenyl]pyridin-2-yl}cyclobutanol. 1H NMR (500 MHz, CDCl3) δ 8.30-8.23 (m, 1H), 7.98-7.95 (m, 1H), 7.93, (t, J=7.2 Hz 1H), 7.79 (t, J=2.2, 1H), 7.74 (d, J=7.8, 1H), 7.66 (d, J=7.8, 1H), 5.36 (s, 1H), 4.03-3.84 (m, 4H), 3.46-3.29 (m, 4H), 2.82-2.47 (m, 4H), 2.27-2.09 (m, 1H), 2.05-1.91 (m, 1H).

Workup

  1. customthe reaction mixture was purged
  2. customflushed with N2(g) (3×)
  3. temperaturecooled to room temperature
  4. additiondiluted with water
  5. extractionextracted with diethyl ether
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationan concentrated under reduced pressure
  10. customThe crude product was purified by silica gel chromatography (ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-8764354602794e96b2b97a97ed28a52b
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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