Sodium Hydroxide → 1-[Bis(4-chlorophenyl)methyl]-3-[1-(3,5-difluorophenyl)-2,2-dimethylpropylidene]azetidine

HRID 1724208Notes

Reaction equation

HRID 1724208 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)[N:9]2[CH2:12][CH:11]([C:13]([C:19]3[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=3)(O)[C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:10]2)=[CH:4][CH:3]=1.CCN(S(F)(F)F)CC.C([O-])(O)=O.[Na+].[OH-].[Na+]>C(Cl)Cl>[Cl:33][C:30]1[CH:29]=[CH:28][C:27]([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:19]3[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=3)[C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:10]2)=[CH:32][CH:31]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 123472(Diethylamino)sulfur trifluoride2×HCID 516892Sodium BicarbonateHCID 111793371-{1-[Bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-(3,5-difluorophenyl)-2,2-dimethylpropan-1-ol

Product 1

HCID 112367991-[Bis(4-chlorophenyl)methyl]-3-[1-(3,5-difluorophenyl)-2,2-dimethylpropylidene]azetidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 80 mg (0.163 mmol) of 1-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-(3,5-difluorophenyl)-2,2-dimethylpropan-1-ol (2) in 1 mL of CH2Cl2, 86 uL (0.653 mmol) of DAST was added and it was stirred for 1 h at −78° C. and overnight at rt. Then another 86 uL (0.653 mmol) of DAST was added again and it was stirred 3 h at 38-45° C. Then to the reaction mixture was added 20 mL of CH2Cl2 and 10 mL of ag NaHCO3. The pH was adjusted to 8-9 with 2N NaOH. The water layer was extracted with CH2Cl2 (3×20 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 the title compound as a white solid; 1H-NMR(CDCl3) δ 1.06 (s, 9R), 3.37 (s, 2H), 4.05 (s, 2H), 4.44 (s, 1H), 6.55 (d, J=8 Hz, 2H), 6.67 (m, 1H), 7.25 (d, J=6.6 Hz, 4H), 7.33 (d, J=7 Hz, 4H); Mass Spectrum: m/e=472 (M+1 35Cl, 35Cl) and 474 (M+1 35Cl, 37Cl).

Workup

  1. stirringit was stirred 3 h at 38-45° C
  2. extractionThe water layer was extracted with CH2Cl2 (3×20 mL)
  3. dry with materialThe combined organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-272ac90ad909450d9a4982a518331f83
Source dataset
uspto-grants-2009_02
Patent number
US07485732B2

Reaction notes

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