Sodium hydride → 4-{4-[2-(Quinazolin-4-yloxy)ethyl]phenyl}butyric acid methyl ester

HRID 1751816Notes

Reaction equation

HRID 1751816 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[H-].[Na+].[CH3:14][O:15][C:16](=[O:29])[CH2:17][CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][OH:28])=[CH:22][CH:21]=1>O1CCCC1.C(OCC)(=O)C>[CH3:14][O:15][C:16](=[O:29])[CH2:17][CH2:18][CH2:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:26][CH2:27][O:28][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 788644-ChloroquinazolineHCID 596786304-[4-(2-Hydroxyethyl)phenyl]butyric acid methyl ester

Product 1

HCID 596786664-{4-[2-(Quinazolin-4-yloxy)ethyl]phenyl}butyric acid methyl esterYield 43%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A dry 50 mL flask was fitted with an addition funnel. To the flask were added 4-chloroquinazoline (592 mg, 3.6 mmol), anhydrous tetrahydrofuran (10 mL), and 60 wt % sodium hydride (187 mg, 4.7 mmol). A solution of Example 1B (800 mg, 3.6 mmol) in anhydrous tetrahydrofuran (10 mL) was added dropwise using the addition funnel. The reaction was stirred for 3.5 hours. The reaction was diluted with ethyl acetate and quenched by the addition of aqueous 0.1 N hydrochloric acid. The mixture was transferred to a separatory funnel and washed with brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated. Column chromatography [silica gel; eluent hexanes-ethyl acetate (4:1)] provided the desired product (538 mg, 43%). 1H(CDCl3) δ(ppm): 1.92-1.98 (m, 2H); 2.33 (t, 2H); 2.64 (t, 2H); 3.19 (t, 2H); 3.66 (s, 3H); 4.79 (t, 2H); 7.15 (d, 2H); 7.27 (d, 2H); 7.57 (t, 1H); 7.83 (t, 1H); 7.94 (d, 1H); 8.15 (d, 1H); 8.80 (s, 1H). 26.68, 33.59, 34.93, 35.03, 51.67, 67.89, 116.48, 123.72, 127.23, 127.82, 128.87, 129.24, 133.74, 135.76, 139.90, 151.08, 154.56, 166.89, 174.10.

Workup

  1. customA dry 50 mL flask was fitted with an addition funnel
  2. customquenched by the addition of aqueous 0.1 N hydrochloric acid
  3. customThe mixture was transferred to a separatory funnel
  4. washwashed with brine
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-e738526a7f7246e8bcc9364b42f68fba
Source dataset
uspto-grants-2015_10
Patent number
US09161997B2

Reaction notes

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