Ethyl 4-chloroquinazoline-2-carboxylate → (4-Chloroquinazolin-2-yl)(4-fluorophenyl)methanone

HRID 625733

Reaction equation

HRID 625733 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][CH:19]=1>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])=[CH:19][CH:20]=2)=[O:14])[N:3]=1

Participants

4

Reactant 2

HCID 3477840Ethyl 4-chloroquinazoline-2-carboxylateHCID 178418676HCID 178418676, compound

Product 1

HCID 86649048(4-Chloroquinazolin-2-yl)(4-fluorophenyl)methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl 4-chloroquinazoline-2-carboxylate (0.6 g, 2.53 mmol) in THF (6 mL) at −40° C., was added dropwise a 1 M solution of 4-fluorophenylmagnesium bromide in THF (3 mL, 3.0 mmol, 1.2 eq). The mixture was stirred at −40 C for 4 h. The reaction was quenched by adding 0.5 N HCl solution (5 mL) and the mixture was extracted with EtOAc (2×10 mL). The combined organic layers were washed with brine and dried over MgSO4. The crude product was purified on a silica gel column using a mixture of EtOAc-hexanes as eluent. (4-chloroquinazoline-2-yl)(4-fluorophenyl)methanone was obtained as a light yellow solid (440 mg, 60%). 1H NMR (300 MHz, DMSO-d6) δ 7.45-740 (m, 2H), 8.07-8.03 (m, 1H), 8.17-8.13 (m, 2H), 8.23 (m, 2H), 8.42 (d, 1H); LC-MS (ESI) m/z 287 (M+H)+.

Workup

  1. customThe reaction was quenched
  2. additionby adding 0.5 N HCl solution (5 mL)
  3. extractionthe mixture was extracted with EtOAc (2×10 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. customThe crude product was purified on a silica gel column
  7. additiona mixture of EtOAc-hexanes as eluent

Sources & evidence

ORD record
ord-e9d6339c125e473c9ffd864a059512e7
Source dataset
uspto-grants-2016_04
Patent number
US09308207B2

Linked notes

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