Diethyl Ether → 1-{1-[Bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-1-(3,5-difluorophenyl)-2-methylpropan-2-ol

HRID 602662Notes

Reaction equation

HRID 602662 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)[N:9]2[CH2:12][C:11](=[C:13]([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=3)C(OC)=O)[CH2:10]2)=[CH:4][CH:3]=1.[CH3:33][Li].C([O:37][CH2:38][CH3:39])C>>[Cl:32][C:29]1[CH:28]=[CH:27][C:26]([CH:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[N:9]2[CH2:12][C:11](=[C:13]([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=3)[C:38]([CH3:39])([OH:37])[CH3:33])[CH2:10]2)=[CH:31][CH:30]=1

Participants

4

Reactant 3

HCID 3283Diethyl Ether3×HCID 57559907Methyl {1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(3,5-difluorophenyl)acetateHCID 178418348HCID 178418348, compound2×

Product 1

HCID 113519591-{1-[Bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-1-(3,5-difluorophenyl)-2-methylpropan-2-ol

Conditions

Temperature
-78 °C

Procedure

A solution of 1.15 g (2.43 mmol) of methyl {1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(3,5-difluorophenyl)acetate (Preparation 5) in 10 mL of dry ethyl ether was cooled to −78° C. under nitrogen. Dropwise, 3.1 mL of a 1M solution of methyllithium in ether was added. After 30 minutes, another 3.1 mL of the 1M solution of methyllithium in ether was added dropwise and the solution was stirred at −78° C. for 30 min. The reaction was quenched by addition of water and the mixture was partitioned between ether and water. The aqueous extract was washed with ether and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The residue was purified by chromatography on a Waters RCM column (5 micron silica gel, 20 mm×10 cm) using a 2:1 mixture of hexane and 5:4:1 hexane-methyl tert-butyl ether-acetonitrile. Homogenous fractions were pooled and concentrated to afford the title compound; 1NMR (CDCl3) δ 1.35 (s, 3H), 3.49 (m, 2H), 4.09 (m, 2H), 4.46 (s, 1H), 6.68 (m, 1H), 6.70 (m, 1H), 7.26 (m, 4H), 7.34 (m, 4H); Mass Spectrum: m/e=474 (M+1 35Cl, 35Cl) and 476 (M+1 35Cl, 37Cl).

Workup

  1. customThe reaction was quenched by addition of water
  2. customthe mixture was partitioned between ether and water
  3. extractionThe aqueous extract
  4. washwas washed with ether
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on a Waters RCM column (5 micron silica gel, 20 mm×10 cm)
  9. additiona 2:1 mixture of hexane and 5:4:1 hexane-methyl tert-butyl ether-acetonitrile
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-84ce6cc7031a4efc8f95abf591fd8482
Source dataset
uspto-grants-2011_03
Patent number
US07906503B2

Reaction notes

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