Sodium Hydroxide → HCID 67055313, compound

HRID 603010Notes

Reaction equation

HRID 603010 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][N:16]([C@@H:18]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)[C:19]3[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=3)[C:22]#[N:23])[CH2:15]2)[C:10](O)([CH3:12])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.N1C=CC=CC=1.[FH:40].[OH-].[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.O.ClCCCl>[Br:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][N:16]([C@@H:18]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)[C:19]3[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=3)[C:22]#[N:23])[CH2:15]2)[C:10]([F:40])([CH3:12])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 64774Pyridine, hydrofluoride (1:1)HCID 516892Sodium BicarbonateHCID 67055395HCID 67055395, compound

Product 1

HCID 67055313HCID 67055313, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
41 °C

Procedure

A mixture of 6.90 g (13.07 mmol) of 3-[(S)-{3-[(1S)-1-(3-bromo-5-fluorophenyl)-2-hydroxy-2-methylpropyl]azetidin-1-yl}(4 chlorophenyl)methyl]benzonitrile, 50 mL of hydrogen fluoride pyridine (HF 70%), and 60 mL of 1,2-dichloroethane was stirred at 40-42° C. for 16 h. Then the reaction mixture was poured slowly to a mixture of 250 mL of water, 74 g of NaOH, 300 mL of aq NaHCO3, 300 g of ice and 500 mL of CH2Cl2 with rapid stirring. The pH of the mixture was adjusted to 7-8, and the mixture was filtered to remove solids. The aqueous layer was extracted with three 300 mL portions of CH2Cl2. The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography with hexane/ethyl acetate to afford the title compound as a white solid; 1H-NMR(CDCl3) δ 1.25 (t, 6H, J=11.8 Hz), 2.32(t, 1H, J=7.5 Hz), 2.83-2.89(m, 2H), 3.09-3.17(m, 2H), 3.59 (m, 1H), 4.26(s, 1H), 6.85 (d, 1H, J=9.1 Hz), 7.10-7.14(m, 2H), 7.28-7.33 (m, 4H), 7.36 (t, 1H, J=7.2 Hz), 7.46 (d, 1H, J=7.8 Hz), 7.56 (d, 1H, J=7.7 Hz), 7.67 (s, 1H); Mass Spectrum: m/e=529, (M+1, 35Cl 79Br), 531 (M+1, 37Cl79Br/35Cl 81Br), 533 (M+1, 37Cl81Br).

Workup

  1. filtrationthe mixture was filtered
  2. customto remove solids
  3. extractionThe aqueous layer was extracted with three 300 mL portions of CH2Cl2
  4. dry with materialThe combined organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography with hexane/ethyl acetate

Sources & evidence

ORD record
ord-6acc5958f84a4805ae989e8c5959be67
Source dataset
uspto-grants-2011_03
Patent number
US07906652B2

Reaction notes

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