1-Propanol → HCID 178466787, compound

HRID 1161176Notes

Reaction equation

HRID 1161176 reaction equation
Br[CH2:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15](=[O:17])[CH3:16])=[C:11]([OH:18])[C:10]=2[Cl:19])=[CH:5][CH:4]=1.[OH:22][C:23]1[CH:27]=[C:26]([C:28]2[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=2)[O:25][N:24]=1.C([O-])([O-])=O.[Na+].[Na+].C(O)CC>O.C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:22][C:23]1[CH:27]=[C:26]([C:28]2[CH:33]=[C:32]([CH:31]=[CH:30][CH:29]=2)[CH2:2][C:3]2[CH:21]=[CH:20][C:6]([CH2:7][O:8][C:9]3[CH:14]=[CH:13][C:12]([C:15](=[O:17])[CH3:16])=[C:11]([OH:18])[C:10]=3[Cl:19])=[CH:5][CH:4]=2)[O:25][N:24]=1

Participants

8

Reactant 4

HCID 10311-PropanolHCID 10340Sodium CarbonateHCID 574384161-(4-((4-(Bromomethyl)benzyl)oxy)-3-chloro-2-hydroxyphenyl)ethanoneHCID 178514831HCID 178514831, compound

Product 1

HCID 178466787HCID 178466787, compoundYield 5.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

Add 1-(4-(4-(bromomethyl)benzyloxy)-3-chloro-2-hydroxyphenyl)ethanone (180 mg, 0.487 mmol) and 3-(3-hydroxyisoxazol-5-yl)phenylboronic acid (218 mg, 1.06 mmol) to a 2.0 M solution of Na2CO3 in water (2.36 mL), dimethoxyethane (4.72 mL), and n-PrOH (4.72 mL). Degas the solution. Add tetrakis(triphenylphosphine)palladium (0) (123 mg, 0.106 mmol) and degas the mixture. Heat the mixture at 70° C. for 12 h. Quench the reaction with water. Extract with EtOAc. Dry, filter and concentrate. Purify the residue by flash chromatography on silica gel afforded the title compound (12 mg, 5%): 1H NMR (d6-DMSO) δ 2.61 (s, 3H), 4.02 (s, 2H), 5.31 (s, 2H), 6.51 (s, 1H), 6.89 (d, J=9.0 Hz, 1H), 7.31-7.36 (m, 3H), 7.39-7.44 (m, 3H), 7.62 (d, J=7.8 Hz, 1H), 7.70 (s, 1H), 7.93 (d, J=9.4 Hz, 1H), 11.34 (s, 1H), 13.13 (s, 1H); MS (APCI-neg mode) m/z (rel intensity): 448 (M−H, 100%).

Workup

  1. customDegas the solution
  2. customQuench
  3. customthe reaction with water
  4. extractionExtract with EtOAc
  5. customDry
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify the residue by flash chromatography on silica gel

Sources & evidence

ORD record
ord-5138a557b545476cabcf4cceb7cfdbf5
Source dataset
uspto-grants-2010_10
Patent number
US07816523B2

Reaction notes

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