Sodium sulfate decahydrate → HCID 11751892, compound

HRID 1724176Notes

Reaction equation

HRID 1724176 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)[N:9]2[CH2:12][CH:11]([CH:13]([C:17]3[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[CH:18]=3)[C:14]([CH3:16])=[O:15])[CH2:10]2)=[CH:4][CH:3]=1.[CH3:32][Mg]Cl.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>C1COCC1>[Cl:31][C:28]1[CH:27]=[CH:26][C:25]([CH:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[N:9]2[CH2:12][CH:11]([CH:13]([C:17]3[CH:18]=[C:19]([F:24])[CH:20]=[C:21]([F:23])[CH:22]=3)[C:14]([CH3:32])([OH:15])[CH3:16])[CH2:10]2)=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 62649Sodium sulfate decahydrateHCID 11328654HCID 11328654, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 11751892HCID 11751892, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 230 mg (0.5 mmol) of 1-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-(3,5-difluorophenyl)acetone in 10 mL of THF was added slowly a solution of 0.42 mL (1.25 mmol) of methylmagnesium chloride (3.0M solution in THF) at −78° C. and stirred for 1 h. The reaction mixture was warmed to 0° C. for 1 h, followed by adding 1 g of sodium sulfate decahydrate to quench the reaction, and stirring for 1 h at rt. The quenched reaction mixture was filtered and the organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography with hexanes/acetone=8:1 to afford racemic 1-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-(3,5-difluorophenyl)-2-methylpropan-2-ol as a white solid. The enantiomers were separated by a chiral column (OJ Column with hexanes/ethyl alcohol); 1H NMR(CDCl3) δ 1.06 (s, 3H), 1.15 (S, 3H), 2.29 (t, 1H, J=7.5 Hz), 6.73 (m, 3H), 7.21-7.33 (m, 8H); Mass Spectrum: m/e=476 (M+1 35Cl, 35Cl) and 478 (M+1 35Cl, 37Cl).

Workup

  1. customto quench
  2. customthe reaction
  3. stirringstirring for 1 h at rt
  4. customThe quenched reaction mixture
  5. filtrationwas filtered
  6. dry with materialthe organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography with hexanes/acetone=8:1

Sources & evidence

ORD record
ord-ac5b050b3c3843539894b8bdb4b89142
Source dataset
uspto-grants-2009_02
Patent number
US07485732B2

Reaction notes

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