Dichloromethane → HCID 11431476, compound

HRID 602701Notes

Reaction equation

HRID 602701 reaction equation
Cl[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][CH:11]([CH:13]([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=3)[C:14]([CH3:17])([OH:16])[CH3:15])[CH2:10]2)=[CH:4][CH:3]=1.N1C=CC=CC=1.F.[OH-].[Na+].C([O-])(O)=O.[Na+].C(Cl)[Cl:48]>>[Cl:48][C:7]1[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][CH:11]([CH:13]([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=3)[C:14]([CH3:15])([OH:16])[CH3:17])[CH2:10]2)[CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 5

HCID 6344Dichloromethane2×HCID 14798Sodium Hydroxide2×HCID 64774Pyridine, hydrofluoride (1:1)HCID 516892Sodium BicarbonateHCID 11751892HCID 11751892, compound

Product 1

HCID 11431476HCID 11431476, compound

Conditions

Temperature
42 °C

Procedure

To a solution of 175 mg (0.368 mmol) of 1-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-(3,5-difluorophenyl)-2-methylpropan-2-ol (1) in 3 mL of CH2Cl2 1 mL of hydrogen fluoride-pyridine was added. The reaction was stirred for 9 h at 42° C. Then the reaction mixture was poured to 7 mL of 5N NaOH, 7 mL of aq NaHCO3 and 30 mL of CH2Cl2. 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/methyl tert-butyl ether to afford the title compound as a white solid; 1NMR (CDCl3) δ 1.25 (t, J=22 Hz, 6H), 2.33 (t, J=6.5 Hz, 1H), 2.83-2.89 (m, 2H), 3.09-3.11 (m, 2H), 3.60 (m, 1H), 4.20 (s, 1H), 6.68-6.71 (m, 3H), 7.21-7.33 (m, 8H); Mass Spectrum: m/e=478 (M+1 35Cl, 35Cl) and 480 (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/methyl tert-butyl ether

Sources & evidence

ORD record
ord-5517bcec68a24d39aebe451e0fbb91ce
Source dataset
uspto-grants-2011_03
Patent number
US07906503B2

Reaction notes

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