Tetrahydrofuran → 1-[3-Bromo-5-chloro-4-methyl-2-(2-morpholin-4-ylethoxy)phenyl]ethanone

HRID 510920Notes

Reaction equation

HRID 510920 reaction equation
[Br:1][C:2]1[C:3]([OH:13])=[C:4]([C:10](=[O:12])[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:33]1([CH2:39][CH2:40]O)[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.O1CCCC1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>>[Br:1][C:2]1[C:3]([O:13][CH2:40][CH2:39][N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[C:4]([C:10](=[O:12])[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8]

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 611632-MorpholinoethanolHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 120274791-(3-Bromo-5-chloro-2-hydroxy-4-methylphenyl)ethanone

Product 1

HCID 866668331-[3-Bromo-5-chloro-4-methyl-2-(2-morpholin-4-ylethoxy)phenyl]ethanoneYield 31%

Conditions

Temperature
-10 °C

Procedure

A solution of 1-(3-bromo-5-chloro-2-hydroxy-4-methylphenyl)ethanone (34 mg, 0.13 mmol), triphenylphosphine (47 mg, 0.18 mmol), and 4-morpholineethanol (23 μL, 0.19 mmol) in tetrahydrofuran (0.38 mL, 4.6 mmol) at −10° C. was treated with diisopropyl azodicarboxylate (35 μL, 0.18 mmol) dropwise and stirred at −10° C. for 15 min and warmed to 20° C. for 30 minutes. The reaction mixture was concentrated, diluted with ethyl acetate (5 mL), and washed with water and brine, dried with magnesium sulfate, filtered, and concentrated to a crude oil. Purification by flash column chromatography using ethyl acetate in hexanes (0%-60%) gave the desired product (15 mg, 31%). LCMS for C15H20BrClNO3 (M+H)+: m/z=376.0, 378.0. Found: 375.9, 378.0.

Workup

  1. temperaturewarmed to 20° C. for 30 minutes
  2. concentrationThe reaction mixture was concentrated
  3. additiondiluted with ethyl acetate (5 mL)
  4. washwashed with water and brine
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to a crude oil
  8. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-d56dea20eaf646568cdb8bb6f7c72095
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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