Hydrochloric Acid → 1-[4-(4-{fluoro-[3-(1H-tetrazol-5-yl)-phenyl]-methyl}-benzyloxy)-2-hydroxy-3-propyl-phenyl]-ethanone

HRID 1818500Notes

Reaction equation

HRID 1818500 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]([CH2:28][CH2:29][CH3:30])[C:5]=1[OH:31])(=[O:3])[CH3:2].[N-:32]=[N+:33]=[N-:34].[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:34][N:33]=[N:32][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:31])[C:6]=2[CH2:28][CH2:29][CH3:30])=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 13387N-methyl-2-pyrrolidoneHCID 33557Sodium AzideHCID 666995833-{[4-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-fluoro-methyl}-benzonitrile

Product 1

HCID 1784396501-[4-(4-{fluoro-[3-(1H-tetrazol-5-yl)-phenyl]-methyl}-benzyloxy)-2-hydroxy-3-propyl-phenyl]-ethanone

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalystHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 3-{[4-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-fluoro-methyl}-benzonitrile (4.7 g, 11.26 mmol), zinc (II) bromide (10.1 g, 45 mmol), sodium azide (5.85 g, 90 mmol), and N-methylpyrrolidinone (50 ml) is heated to 140° C. and stirred 1 hr. The reaction is cooled to room temperature and diluted with water (200 mL). The pH is adjusted to 2 with 5N aqueous hydrochloric acid and extracted with ethyl acetate (3×100 mL). The extracts are combined, dried over magnesium sulfate, filtered, and concentrated. The residue is purified via reversed phase C18 chromatography eluting with 4:6 acetonitrile:(0.1% trifluoroacetic acid) water to 7:3 acetonitrile:(0.1% trifluoroacetic acid) water in 8 runs to give 3.08 g, 59%, of the title compound as fine white needles. 1H NMR (DMSO-d6) δ 12.86 (s, 1H), 8.13 (s, 1H), 8.03 (d, 1H), 7.81 (d, 1H), 7.61-7.70 (m, 2H), 7.48 (m, 4H), 6.78-6.93 (d, 1H), 6.72 (d, 1H), 5.29 (s, 2H), 2.58-2.63 (m, 5H), 1.46-1.53 (m, 2H), 0.88 (t, 3H). LCMS M−1 459.

Workup

  1. temperatureThe reaction is cooled to room temperature
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified via reversed phase C18 chromatography
  7. washeluting with 4:6 acetonitrile
  8. custom(0.1% trifluoroacetic acid) water to 7:3 acetonitrile:(0.1% trifluoroacetic acid) water in 8 runs to give 3.08 g, 59%

Sources & evidence

ORD record
ord-944a99a68de942a9bdec25fd9110058c
Source dataset
uspto-grants-2009_10
Patent number
US07598423B2

Reaction notes

Loading…