Methyl 2-(3,5-difluorophenyl)acetate → Methyl{1-[bis(4-chlorophenyl)methyl]-3-hydroxyazetidin-3-yl}(3,5-difluorophenyl)acetate

HRID 1724168Notes

Reaction equation

HRID 1724168 reaction equation
C([Li])CCC.[F:6][C:7]1[CH:8]=[C:9]([CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH:10]=[C:11]([F:13])[CH:12]=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=2)[N:27]2[CH2:30][C:29](=[O:31])[CH2:28]2)=[CH:22][CH:21]=1>CCCCCC.C1COCC1>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=2)[N:27]2[CH2:28][C:29]([CH:14]([C:9]3[CH:8]=[C:7]([F:6])[CH:12]=[C:11]([F:13])[CH:10]=3)[C:15]([O:17][CH3:18])=[O:16])([OH:31])[CH2:30]2)=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 22270748Methyl 2-(3,5-difluorophenyl)acetateHCID 225066481-[Bis(4-chlorophenyl)methyl]azetidin-3-oneHCID 178418339Butyllithium

Product 1

HCID 67055297Methyl{1-[bis(4-chlorophenyl)methyl]-3-hydroxyazetidin-3-yl}(3,5-difluorophenyl)acetate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 2 mL of 1.6M butyllithium in hexane and 2 mL of dry THF was cooled to −78° C. under nitrogen. To this was added a solution of 0.626 g (3.2 mmol) of methyl (3,5-difluorophenyl)acetate in 4 mL of THF and the solution was stirred at −78° C. After 20 min, a solution of 0.600 g (1.95 mmol) of 1-[bis(4-chlorophenyl)methyl]azetidin-3-one in 4 mL THF was added and the solution was stirred at −78° C. After 1 h, the reaction was quenched by addition of 10 mL of saturated NH4Cl solution and 20 mL of ether. The layers were separated and the aqueous layer was washed with ether. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated. The residue was filtered through a plug of silica gel using 25% ether-hexane to afford the title compound; 1NMR(CDCl3) δ 2.91 (d, 1H J=8.3 Hz), 3.14 (d, 1H J=8.0 Hz), 3.17 (d, 2H, J=8.2 Hz), 3.32 (d, 1H J=7.8 Hz), 3.74 (s, 3H), 4.03 (s, br, 1H), 4.42 (s, 1H), 4.42 (s, 1H), 6.76 (m, 1H), 6.6.89 (m, 2H), 7.33 (m, 4H), 7.38 (m, 4H); Mass Spectrum: m/e=492 (M+1 35Cl, 35Cl ) and 494 (M+1 35Cl, 37Cl).

Workup

  1. stirringthe solution was stirred at −78° C
  2. waitAfter 1 h
  3. customthe reaction was quenched by addition of 10 mL of saturated NH4Cl solution and 20 mL of ether
  4. customThe layers were separated
  5. washthe aqueous layer was washed with ether
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. filtrationThe residue was filtered through a plug of silica gel using 25% ether-hexane

Sources & evidence

ORD record
ord-6b7f1c4531574395b5e37bc68c645a4e
Source dataset
uspto-grants-2009_02
Patent number
US07485732B2

Reaction notes

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