Ammonium Chloride → HCID 86649068, compound

HRID 625821Notes

Reaction equation

HRID 625821 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([O:14]CC)=O)[N:3]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([Mg]Br)=[CH:20][C:19]=1[O:26][CH3:27].CC1CCCO1.[Cl-].[NH4+]>C1COCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([C:21]2[CH:22]=[CH:23][C:18]([F:17])=[C:19]([O:26][CH3:27])[CH:20]=2)=[O:14])[N:3]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 3477840Ethyl 4-chloroquinazoline-2-carboxylateHCID 178426731HCID 178426731, compound2×

Product 1

HCID 86649068HCID 86649068, compoundYield 62.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-35 °C

Procedure

To a stirred mixture of ethyl 4-chloroquinazoline-2-carboxylate (500 mg, 2.11 mmol) in THF (17 mL) at −40° C. was added dropwise 1 M 4-fluoro-3-methoxyphenylmagnesium bromide/2-methyltetrahydrofuran (2.53 mL, 2.53 mmol). The reaction mixture was stirred at −30 to −40° C. for 3 h. Additional 1 M 4-fluoro-3-methoxyphenylmagnesium bromide/2-methyltetrahydrofuran (1.05 mL, 1.05 mmol) was added and stirring was continued at −30 to −40° C. for an additional 1.5 h. To the mixture was added saturated aq ammonium chloride (25 mL) and the mixture was allowed to warm to rt. The mixture was extracted with EtOAc (2×) and the combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was triturated with diethyl ether and the resulting solid was collected by filtration and dried to afford (4-chloroquinazolin-2-yl)(4-fluoro-3-methoxyphenyl)methanone as a colorless solid (417 mg, 62%). 1H NMR (300 MHz, DMSO-d6) δ ppm 3.92 (s, 3H), 7.42 (dd, J=11.1, 8.7 Hz, 1H), 7.64 (m, 1H), 7.85 (d, J=8.4 Hz, 1H), 8.04 (m, 1H), 8.23-8.25 (m, 2H), 8.43 (d, J=8.4 Hz, 1H); LC-MS (ESI) m/z 317 (M+H)+.

Workup

  1. stirringstirring
  2. waitwas continued at −30 to −40° C. for an additional 1.5 h
  3. temperatureto warm to rt
  4. extractionThe mixture was extracted with EtOAc (2×)
  5. dry with materialthe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was triturated with diethyl ether
  9. filtrationthe resulting solid was collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-e30b1fdec0c94c9289db866999906c49
Source dataset
uspto-grants-2016_04
Patent number
US09308207B2

Reaction notes

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