Sodium Azide → (R)-2-azidomethyl-8-(2-methoxyphenyl)-6-fluoro-chroman

HRID 902336Notes

Reaction equation

HRID 902336 reaction equation
CC1C=CC(S(O[CH2:12][C@H:13]2[CH:22]=[CH:21][C:20]3[C:15](=[C:16]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[O:30][CH3:31])[CH:17]=[C:18]([F:23])[CH:19]=3)[O:14]2)(=O)=O)=CC=1.[N-:32]=[N+:33]=[N-:34].[Na+]>CN(C=O)C>[N:32]([CH2:12][C@H:13]1[CH2:22][CH2:21][C:20]2[C:15](=[C:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:30][CH3:31])[CH:17]=[C:18]([F:23])[CH:19]=2)[O:14]1)=[N+:33]=[N-:34]

Participants

4

Reactant 2

HCID 33557Sodium AzideHCID 86609125((R)-8-(2-methoxyphenyl)-6-fluoro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 86609113(R)-2-azidomethyl-8-(2-methoxyphenyl)-6-fluoro-chromanYield 90.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution ((R)-8-(2-methoxyphenyl)-6-fluoro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate (300 mg, 0.67 mmol) and sodium azide (0.22 g, 3.4 mmol) in anhydrous DMF (20 mL) was heated to 90° C. under nitrogen for 20 hours. The cooled reaction mixture was quenched by the addition of water (30 mL) and the resulting suspension stirred vigorously for 10 minutes. The mixture was then partitioned between ethyl acetate (100 mL) and water (100 mL), the organic phase separated, washed with water (100 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Chromatography with 0–30% ethyl acetate in hexanes afforded 190 mg (90%) of (2R)-2-azidomethyl-8-(2-methoxy-phenyl)-6-fluoro-chroman as a colorless oil.

Workup

  1. customThe cooled reaction mixture
  2. customwas quenched by the addition of water (30 mL)
  3. customThe mixture was then partitioned between ethyl acetate (100 mL) and water (100 mL)
  4. customthe organic phase separated
  5. washwashed with water (100 mL) and saturated brine (100 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-eccfb132fbad46719b87ae525c02486c
Source dataset
uspto-grants-2008_04
Patent number
US07365095B2

Reaction notes

Loading…