Methanol → HCID 53873990, compound

HRID 1493605Notes

Reaction equation

HRID 1493605 reaction equation
[CH3:1][O:2][C:3](=[O:14])[CH2:4][NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[CH:7]=1.[N:15]([O-])=O.[Na+].CO.ClCCl>C(O)(=O)C.[Zn].O>[CH3:13][O:12][C:8]1[CH:7]=[C:6]([N:5]([CH2:4][C:3]([O:2][CH3:1])=[O:14])[NH2:15])[CH:11]=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 22669248HCID 22669248, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 53873990HCID 53873990, compoundYield 15.2%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a cold (0°) solution of N-(3-methoxyphenyl)glycine methyl ester (50 g) in aqueous acetic acid (800 ml) was added dropwise an aqueous solution (200 ml) of sodium nitrite (21.2 g) and the mixture was stirred for 30 min. Methanol (200 ml) was added and the mixture was cooled to -10°. Zinc dust (83.2 g) was added portionwise over 2 h during which time the internal temperature was maintained at -10° to 0° and the mixture was stirred for a further 1 h at 0°. Dichloromethane (800 ml) and water (800 ml) were added and the resulting suspension was filtered. The filtrate was diluted with more water (500 ml) and dichloromethane (500 ml). The phases were separated and the aqueous layer was partitioned with more dichloromethane (2×500 ml). The combined organic extracts were washed with water (3×500 ml) and evaporated in vacuo. The residual oil was treated with 8% sodium bicarbonate (1000 ml) and partitioned with ether (3×700 ml). The combined organic layers were washed with brine (500 ml), dried and evaporated. Purification by FCC eluting with System A (1:1) and then System A (7:3) gave the title compound (8.2 g) as an oil, t.l.c (System A, 1:1) Rf 0.12.

Workup

  1. temperaturethe mixture was cooled to -10°
  2. temperaturewas maintained at -10° to 0°
  3. stirringthe mixture was stirred for a further 1 h at 0°
  4. filtrationthe resulting suspension was filtered
  5. additionThe filtrate was diluted with more water (500 ml) and dichloromethane (500 ml)
  6. customThe phases were separated
  7. customthe aqueous layer was partitioned with more dichloromethane (2×500 ml)
  8. washThe combined organic extracts were washed with water (3×500 ml)
  9. customevaporated in vacuo
  10. additionThe residual oil was treated with 8% sodium bicarbonate (1000 ml)
  11. custompartitioned with ether (3×700 ml)
  12. washThe combined organic layers were washed with brine (500 ml)
  13. customdried
  14. customevaporated
  15. customPurification by FCC
  16. washeluting with System A (1:1)

Sources & evidence

ORD record
ord-b40d767f1df44e998c113de78f4fdc09
Source dataset
uspto-grants-1991_06
Patent number
US05023255

Reaction notes

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