Sodium Azide → HCID 178519573, compound

HRID 1665252Notes

Reaction equation

HRID 1665252 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:19]=[C:20]([CH:30]=[CH:31][CH:32]=2)[C:21]([N:23]2[CH2:27][CH2:26][CH2:25][C@H:24]2[C:28]#[N:29])=[O:22])=[CH:12][CH:11]=1.[N-:33]=[N+:34]=[N-:35].[Na+].Cl.C([NH+](CC)CC)C>C1(C)C=CC=CC=1>[NH:33]1[C:28]([C@@H:24]2[CH2:25][CH2:26][CH2:27][N:23]2[C:21]([C:20]2[CH:30]=[CH:31][CH:32]=[C:18]([CH2:17][O:16][C:13]3[CH:12]=[CH:11][C:10]([C:3]4[CH:4]=[C:5]([F:9])[C:6]([F:8])=[CH:7][C:2]=4[F:1])=[CH:15][CH:14]=3)[CH:19]=2)=[O:22])=[N:29][N:35]=[N:34]1

Participants

5

Reactant 3

HCID 33557Sodium AzideHCID 21900368Triethylammonium hydrochlorideHCID 67150366HCID 67150366, compound

Product 1

HCID 178519573HCID 178519573, compoundYield 81.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

(S)-1-[3-(2′,4′,5′-Trifluoro-biphenyl-4-yloxymethyl)-benzoyl]-pyrrolidine-2-carbonitrile (1.56 g, 3.47 mmol), sodium azide (678 mg, 10.43 mmol) and triethylammonium hydrochloride (1.43 g, 10.43 mmol) in toluene were heated at 100° C. for 17 hrs. The reaction mixture was cooled, concentrated and distributed between 20 mL 0.5N HCl and 100 mL ethyl acetate. The ethyl acetate layer was separated, washed with saturated NaCl, dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography with a 0-40% gradient of ethyl acetate/MeOH/AcOH (95:5:1) in CH2Cl2 to give 1.35 g (81.2%) of [(S)-2-(1H-tetrazol-5-yl)-pyrrolidin-1-yl]-[3-(2′,4′,5′-trifluoro-biphenyl-4-yloxymethyl)-phenyl]-methanone as a white solid. LC-MS (ES) calculated for C25H20F3N5O2, 479.47; found m/z 480.1 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated
  3. customThe ethyl acetate layer was separated
  4. washwashed with saturated NaCl
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography with a 0-40% gradient of ethyl acetate/MeOH/AcOH (95:5:1) in CH2Cl2

Sources & evidence

ORD record
ord-bdb09b6939f643edb164bff83b0b76b2
Source dataset
uspto-grants-2011_10
Patent number
US08039495B2

Reaction notes

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