Hydrochloric Acid → HCID 178466788, compound

HRID 1818502Notes

Reaction equation

HRID 1818502 reaction equation
[C:1]([C:4]1[CH:27]=[CH:26][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16]([F:25])[C:17]3[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=3)[C:20]#[N:21])=[CH:12][CH:11]=2)=[C:6]([CH3:28])[C:5]=1[OH:29])(=[O:3])[CH3:2].[N-:30]=[N+:31]=[N-:32].[Na+].CN1CCCC1=O.Cl>O.[Br-].[Zn+2].[Br-]>[F:25][CH:16]([C:17]1[CH:24]=[CH:23][CH:22]=[C:19]([C:20]2[NH:32][N:31]=[N:30][N:21]=2)[CH:18]=1)[C:13]1[CH:12]=[CH:11][C:10]([CH2:9][O:8][C:7]2[CH:26]=[CH:27][C:4]([C:1](=[O:3])[CH3:2])=[C:5]([OH:29])[C:6]=2[CH3:28])=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 13387N-methyl-2-pyrrolidoneHCID 33557Sodium AzideHCID 66699515HCID 66699515, compound

Product 1

HCID 178466788HCID 178466788, compoundYield 22.5%

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalystHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 3-{[4-(4-acetyl-3-hydroxy-2-methyl-phenoxymethyl)-phenyl]-fluoro-methyl}-benzonitrile (400 mg, 1.03 mmol), zinc (II) bromide (280 mg, 1.24 mmol), sodium azide (160 mg, 2.48 mmol) and N-methylpyrrolidinone (10 mL) is stirred at 140° C. 1 hr. The reaction mixture is cooled, diluted with water, and the pH is adjusted to 2 with aqueous hydrochloric acid. The product is extracted with ethyl acetate, dried over magnesium sulfate, filtered, and concentrated. The residue is purified via reversed phase C-18 chromatography eluting with 4:6 acetonitrile:(0.1% trifluoroacetic acid) water to acetonitrile to give the title compound (100 mg, 22%) as a white solid. 1H NMR (DMSO-d6) δ 12.85 (s, 1H), 8.13 (s, 1H), 8.03 (d, 1H), 7.80 (d, 1H), 7.6107.70 (m, 2H), 7.48-7.55 (m, 4H), 6.78-6.94 (d, 1H), 6.73 (d, 1H), 5.29 (s, 2H), 2.59 (s, 3H), 2.05 (s, 3H). LCMS M−1 431.

Workup

  1. custom1 hr
  2. temperatureThe reaction mixture is cooled
  3. extractionThe product is extracted with ethyl acetate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified via reversed phase C-18 chromatography
  8. washeluting with 4:6 acetonitrile

Sources & evidence

ORD record
ord-f9fa5220c07d477fac431a24b51503a3
Source dataset
uspto-grants-2009_10
Patent number
US07598423B2

Reaction notes

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