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

HRID 602699Notes

Reaction equation

HRID 602699 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)[N:9]2[CH2:12][CH:11]([C:13]([C:15]3[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=3)=[O:14])[CH2:10]2)=[CH:4][CH:3]=1.[C:30]([Mg]Cl)([CH3:33])([CH3:32])[CH3:31].CCOCC.[OH-].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:23]2[CH:24]=[CH:25][C:26]([Cl:29])=[CH:27][CH:28]=2)[N:9]2[CH2:12][CH:11]([C:13]([C:15]3[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=3)([OH:14])[C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:10]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 22506671{1-[Bis(4-chlorophenyl)methyl]azetidin-3-yl}(3,5-difluorophenyl)methanoneHCID 178418310HCID 178418310, compound

Product 1

HCID 111793371-{1-[Bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-(3,5-difluorophenyl)-2,2-dimethylpropan-1-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 120 mg (0.278 mmol) of {1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}(3,5-difluorophenyl)methanone (Example 19, Step 4) in 3 mL of THF, 0.35 mL (0.69 mmol) of tert-butyl magnesium chloride (2M in THF) was added and stirred for 1 h at −78° C. Then to the reaction mixture was added 30 μL of ether and 5 mL of 7 mL of qNaHCO3. The pH was adjusted to 8-9 with 2N NaOH. The water layer was extracted with CH2Cl2 (3×30 mL). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography with hexanes/ethyl acetate to afford of the title compound as a white solid; 1H-NMR (CDCl3) δ 0.88 (s, 9H), 2.46 (t, J=7.2 Hz, 1H), 2.97 (s, 1H), 3.05 (t, J=7.6 Hz, 1H), 3.31-3.39 (m, 2H), 3.42 (m, 1H), 4.25 (s, 1H), 6.56 (m, 2H), 6.68 (m, 1H), 7.24-7.36 (m, 8H); Mass Spectrum m/e=490 (M+1 35Cl, 35Cl) and 492 (M+1 35Cl, 37Cl).

Workup

  1. extractionThe water layer was extracted with CH2Cl2 (3×30 mL)
  2. dry with materialThe combined organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-594be8c8528f44b5af4f7c2bdc457870
Source dataset
uspto-grants-2011_03
Patent number
US07906503B2

Reaction notes

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