Dichloromethane → HCID 11983634, compound

HRID 1724204Notes

Reaction equation

HRID 1724204 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][N:16]([CH:18]([C:25]3[CH:30]=[CH:29]C=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:15]2)[C:10]([CH3:13])(O)[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[N:31]1[CH:36]=CC=CC=1.[FH:37].[OH-].[Na+].C([O-])(O)=O.[Na+].[CH2:45]([Cl:47])Cl>>[Cl:47][C:45]1[CH:29]=[CH:30][C:25]([C@H:18]([N:16]2[CH2:17][CH:14]([C@@H:9]([C:4]3[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=3)[C:10]([F:37])([CH3:11])[CH3:13])[CH2:15]2)[C:19]2[CH:24]=[C:23]([CH:22]=[CH:21][CH:20]=2)[C:36]#[N:31])=[CH:26][CH:27]=1

Participants

6

Reactant 5

HCID 6344Dichloromethane2×HCID 14798Sodium Hydroxide2×HCID 64774Pyridine, hydrofluoride (1:1)HCID 516892Sodium BicarbonateHCID 67055316(1S)-1-(3,5-difluorophenyl)-1-[1-(diphenylmethyl)azetidin-3-yl]-2-methylpropan-2-ol

Product 1

HCID 11983634HCID 11983634, compound

Conditions

Temperature
42 °C

Procedure

To a solution of 5.5 g (13.5 mmole) of (1S)-1-(3,5-difluorophenyl)-1-[1-(diphenylmethyl)azetidin-3-yl]-2-methylpropan-2-ol in 25 mL of CH2Cl2 was added 15 mL of hydrogen fluoride-pyridine and the two-phase mixture was stirred for 15 h at 42° C. Then the reaction mixture was poured to 100 mL of 5N NaOH, 20 mL of aq NaHCO3, 150 mL of CH2Cl2 and 100 mL ice. The pH was adjusted to 8-9 with 2N NaOH. The water layer was extracted with CH2Cl2 (3×1500 mL). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography with 10% methyl tert-butyl ether-hexane 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), 4.30 (s, 1H), 6.68-6.71 (m, 3H), 7.21-7.8 (m, 10H); Mass Spectrum: m/e=410 (M+1)

Workup

  1. extractionThe water layer was extracted with CH2Cl2 (3×1500 mL)
  2. dry with materialThe combined organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography with 10% methyl tert-butyl ether-hexane

Sources & evidence

ORD record
ord-9eed7d486676461db160187c0f04d3c2
Source dataset
uspto-grants-2009_02
Patent number
US07485732B2

Reaction notes

Loading…