HCID 19829952, compound → HCID 54312551, compound

HRID 1493628Notes

Reaction equation

HRID 1493628 reaction equation
[CH3:1][O:2][C:3](=[O:14])[CH2:4][NH:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]([CH3:13])[CH:7]=1.[N:15]([O-])=O.[Na+]>C(O)(=O)C.O.[Zn]>[F:12][C:9]1[CH:10]=[CH:11][C:6]([N:5]([CH2:4][C:3]([O:2][CH3:1])=[O:14])[NH2:15])=[CH:7][C:8]=1[CH3:13]

Participants

6

Reactant 2

HCID 19829952HCID 19829952, compound2×HCID 23668193Sodium Nitrite

Product 1

HCID 54312551HCID 54312551, compoundYield 17.4%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent3×

Procedure

N-(4-Fluoro-3-methylphenyl)glycine methyl ester (Intermediate 63, 7.5 g, 0.038 mol) was dissolved in a mixture of glacial acetic acid (60 ml) and water (8 ml) and the solution was cooled to ~5° C. To this was added a solution of sodium nitrite (4.3 g, 0.063 mol) in water (15 ml) at the same low temperature over 20 minutes. Stirring was continued for 1 hour and the temperature was then lowered to between -10° and 0° C. Zinc dust (15.3 g, 0.234 mol) was added at the maintained low temperature and the resulting suspension was stirred at ~0° C. for 4 hours. It was then poured into water (250 ml) and extracted with ethyl acetate (2×200 ml). The extract was washed with 8% sodium bicarbonate solution until all effervescence had ceased. It was then dried (MgSO4) and evaporated to give a brown semi-solid. This was triturated with ether/hexane (1:2, ~15 ml) to give a white solid which was filtered and washed with ice-cold ether. The liquors were evaporated to give a brown oil and this was purified by flash column chromatography on silica (Merck 9385; 225 g) eluting with ether/hexane (1:1) to give the title compound (Intermediate 64) as an orange oil (1.4 g, 17%).

Workup

  1. temperaturethe solution was cooled to ~5° C
  2. customwas then lowered to between -10° and 0° C
  3. stirringthe resulting suspension was stirred at ~0° C. for 4 hours
  4. extractionextracted with ethyl acetate (2×200 ml)
  5. washThe extract was washed with 8% sodium bicarbonate solution until all effervescence
  6. dry with materialIt was then dried (MgSO4)
  7. customevaporated
  8. customto give a brown semi-solid
  9. customThis was triturated with ether/hexane (1:2, ~15 ml)
  10. customto give a white solid which
  11. filtrationwas filtered
  12. washwashed with ice-cold ether
  13. customThe liquors were evaporated
  14. customto give a brown oil
  15. customthis was purified by flash column chromatography on silica (Merck 9385; 225 g)
  16. washeluting with ether/hexane (1:1)

Sources & evidence

ORD record
ord-334fb119264b4bcea6b1d95e7bb39722
Source dataset
uspto-grants-1991_06
Patent number
US05023255

Reaction notes

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