Triethylamine → HCID 23590002, compound

HRID 898431Notes

Reaction equation

HRID 898431 reaction equation
[C:1]1([C:7]2[O:8][C:9]([CH2:15][CH2:16][CH3:17])=[C:10]([CH2:12][CH2:13][OH:14])[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[NH4+].[Cl-].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:38]([O:40][C:41](=[O:53])[C:42]([O:45][C:46]1[CH:51]=[CH:50][C:49](O)=[CH:48][CH:47]=1)([CH3:44])[CH3:43])[CH3:39]>C(Cl)Cl.CN(C=O)C>[CH2:38]([O:40][C:41](=[O:53])[C:42]([CH3:44])([O:45][C:46]1[CH:51]=[CH:50][C:49]([O:14][CH2:13][CH2:12][C:10]2[N:11]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:8][C:9]=2[CH2:15][CH2:16][CH3:17])=[CH:48][CH:47]=1)[CH3:43])[CH3:39]

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 181741Ethyl 2-(4-hydroxyphenoxy)-2-methylpropanoateHCID 22261134HCID 22261134, compound

Product 1

HCID 23590002HCID 23590002, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

2-(2-Phenyl-5-propyloxazol-4-yl)ethanol (225 mg, 0.97 mmol) and triethyl amine (167 mg, 1.65 mmol, 0.23 mL) were dissolved in CH2Cl2 (3.5 mL) at 0° C. and treated with methane sulfonyl chloride (167 mg, 1.46 mmol, 0.11 mL). After 1 h, NH4Cl (25 mL of a 10% aqueous solution) was added and then the organic phase was dried (MgSO4), filtered and concentrated to an oil. The intermediate mesylate was combined with Cs2CO3 (383 mg, 1.18 mmol), and 2-(4-hydroxyphenoxy)-2-methylpropanoic acid ethyl ester (American Home Products U.S. Pat. No. 3,795,691) (190 mg, 0.84 mmol) in DMF (4 mL) and heated to 55° C. After 18 h, the reaction mixture was partitioned between H2O (25 mL) and EtOAc (25 mL) and then the organic phase washed with H2O (2×), dried (MgSO4), filtered and concentrated. The product was purified by flash chromatography (70 mL SiO2, hexanes to 20% EtOAc/hexanes) and obtained as a colorless oil (170 mg, 46%): Rf=0.49 in 20% EtOAc/hexanes; 1H NMR (500 MHz, CDCl3) δ 8.00-7.96 (m, 2H), 7.42-7.38 (m, 3H), 6.83-6.76 (m, 4H), 4.22 (q, J=7.0 MHz, 2H), 4.19 (t, J=7.0 Hz, 2H), 2.95 (t, J=7.0 Hz, 2H), 2.67 (t, J=7.0 Hz, 2H) 1.71 (sextet, J=7.0 Hz, 2H), 1.52 (s, 6H), 1.26 (t, J=7.0 Hz, 3H), 0.96 (t, J=7.0 Hz, 3H).

Workup

  1. dry with materialthe organic phase was dried (MgSO4)
  2. filtrationfiltered
  3. concentrationconcentrated to an oil
  4. waitAfter 18 h
  5. customthe reaction mixture was partitioned between H2O (25 mL) and EtOAc (25 mL)
  6. washthe organic phase washed with H2O (2×)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe product was purified by flash chromatography (70 mL SiO2, hexanes to 20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-077e81f232a04a20b8ef75c9cab5cc4a
Source dataset
uspto-grants-2008_04
Patent number
US07351728B2

Reaction notes

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