Tert-butyl 4-formylbenzoate → HCID 19608778, compound

HRID 1603040Notes

Reaction equation

HRID 1603040 reaction equation
[CH:1]([C:3]1[CH:15]=[CH:14][C:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[CH:5][CH:4]=1)=O.[N:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])=[N+]=[N-].C[O-].[Na+].N(C(=CC1C=CC=CC=1)C([O-])=O)=[N+]=[N-]>CO.O.C1(C)C(C)=CC=CC=1>[CH3:23][O:22][C:20]([C:19]1[NH:16][C:15]2[C:3]([CH:1]=1)=[CH:4][CH:5]=[C:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH:14]=2)=[O:21]

Participants

8

Reactant 4

HCID 2751588Tert-butyl 4-formylbenzoateHCID 4020482Methyl 2-azidoacetateHCID 10942334Sodium MethoxideHCID 131721450HCID 131721450, compound

Product 1

HCID 19608778HCID 19608778, compoundYield 42%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 7237O-XyleneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of t-butyl 4-formylbenzoate (8.52 g, 41 mmol) and methyl azidoacetate [M. S. Allen, L. K. Hamaker, A. J. La Loggia, J. M. Cook, Synth. Commun., 1992, 22, 2077-2102] (28.5 g, 248 mmol) in dry MeOH (200 mL) was added dropwise over 1 h to a solution of NaOMe (60 mL of a 3.3M solution in MeOH, 197 mmol) under nitrogen with cooling in an ice-salt bath. The yellow suspension was stirred for a further 1 h at 0° C., allowed to stand at 4° C. for 15 h, then diluted with water and the solid filtered off and dried in the dark. A solution of this crude azidocinnamate (8.76 g, 29 mmol) in dry xylene (400 mL) was added dropwise over 2 h to xylene (100 mL) at ref lux under nitrogen, the solution stirred at reflux for a further 1 h, then cooled and evaporated. Recrystallisation from MeOH gave t-butyl 2-(methoxycarbonyl)indole-6-carboxylate as a white solid (4.72 g, 42%), mp 189-190.5° C. 1H NMR [(CD3)2SO] δ12.26 (s, 1H, NH), 8.08 (s, 1H, H-3 or H-7), 7.73 (d, J=8.4 Hz, 1H, H-4), 7.61 (dd, J=8.4, 1.3 Hz, 1H, H-5), 7.21 (d, J=1.3 Hz, 1H, H-3 or H-7), 3.89 (s, 3H, CO2Me), 1.56 (s, 9H, CO2 tBu); 13C NMR δ165.5 (Co2 tBu), 161.4 (CO2Me), 136.5, 130.0, 129.9, 127.3 (C-2,6,8,9), 121.9, 120.3, 114.4, 107.5 (C-3,4,5,7), 80.4 (OCMe3), 52.1 (OCH3), 27.8 (tBu). Anal. (C15H17NO4) C,H,N.

Workup

  1. temperaturewith cooling in an ice-salt bath
  2. waitto stand at 4° C. for 15 h
  3. filtrationthe solid filtered off
  4. customdried in the dark
  5. stirringthe solution stirred
  6. temperatureat reflux for a further 1 h
  7. temperaturecooled
  8. customevaporated
  9. customRecrystallisation from MeOH

Sources & evidence

ORD record
ord-a6f0d28d88f24170acffbfe3593878ec
Source dataset
uspto-grants-1999_11
Patent number
US05985909

Reaction notes

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