2-Methyl-2-butene → HCID 21048654, compound

HRID 2211943Notes

Reaction equation

HRID 2211943 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](C)(C)[O:18][SiH2]C(C)C)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:25]1[C:33]2[C:28](=[CH:29][C:30]([Cl:34])=[CH:31][CH:32]=2)[NH:27][N:26]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(C1C=C2C(=CC=1)N(C(OC(C)(C)C)=O)C(C1C3C(=CC=CC=3)NN=1)=C2)=[O:36].CC(=CC)C.OP([O-])(O)=O.[Na+].Cl([O-])=O.[Na+]>ClCCl.C(O)(C)(C)C.[O-2].[O-2].[Mn+4]>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]([OH:36])=[O:18])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:25]1[C:33]2[C:28](=[CH:29][C:30]([Cl:34])=[CH:31][CH:32]=2)[NH:27][N:26]=1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

9

Reactant 5

HCID 105532-Methyl-2-buteneHCID 21963068HCID 21963068, compoundHCID 23668197Sodium Chlorite2×HCID 23672064Monosodium phosphate2×HCID 131725914HCID 131725914, compound

Product 1

HCID 21048654HCID 21048654, compound

Reagents, catalysts & solvents 3

HCID 178418406HCID 178418406, compoundCatalyst2×HCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Procedure

A solution of the alcohol 4-3 (210 mg, 0.528 mmol) in dichloromethane was treated with manganese dioxide (229 mg, 2.64 mmol) and heated to reflux where it remained for 1 h. Five additional equivalents of manganese dioxide were added and the reaction was maintained at reflux for 1 h. The excess manganese dioxide was filtered through Celite and the filter cake was washed with ethyl acetate (40 ml) and methanol (40 ml). The filtrate was concentrated in vacuo to a brown oil (4-4). A solution of the tert-butyl 5-formyl-2-(1H-indazol-3-yl)-1H-indole-1-carboxylate (4-4, 1.2 g, 3.3 mmol), 2-methyl-2-butene (19.9 ml, 188.2 mmol), a 1.9M solution of sodium phosphate monobasic (1.73 ml, 6.6 mmol), and sodium chlorite (597.3 mg, 6.60 mmol) were stirred in t-Butanol for 1 h. 3 additional equivalents of both solid sodium phosphate monobasic and sodium chlorite were added to the reaction over a 3 h period, and the reaction was mixed for 24 h. The t-Butanol was removed in vacuo and the residual yellow solid was dissolved in ethyl acetate (150 ml) and washed twice with a 98:2 mixture of 10% sodium bisulfite:10% potassium bisulfate (2×75 ml). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to afford 1-(tert-butoxycarbonyl)-2-(1H-indazol-3-yl)-1H-indole-5-carboxylic acid (4-5); 1H NMR(500 MHz, CDCl3) δ 8.47 (s, 1H), 8.40 (d, 1H, J=8.8 Hz), 8.17 (d, 1H, J=8.8 Hz), 7.68 (d, 1H, J=8.1 Hz), 7.56 (d, 1H, J=8.3 Hz), 7.46 (t, 1H, J=8.3 Hz), 7.23 (t, 1H, J=7.8 Hz), 6.99 (s, 1H), 1.14 (s, 3H).

Workup

  1. temperatureheated
  2. temperatureto reflux where it
  3. temperaturethe reaction was maintained
  4. temperatureat reflux for 1 h
  5. filtrationThe excess manganese dioxide was filtered through Celite
  6. washthe filter cake was washed with ethyl acetate (40 ml) and methanol (40 ml)
  7. concentrationThe filtrate was concentrated in vacuo to a brown oil (4-4)
  8. additionthe reaction was mixed for 24 h
  9. customThe t-Butanol was removed in vacuo
  10. dissolutionthe residual yellow solid was dissolved in ethyl acetate (150 ml)
  11. washwashed twice with a 98:2 mixture of 10% sodium bisulfite
  12. dry with materialThe combined organics were dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ae039d3a30aa4aac96f63d96830eb200
Source dataset
uspto-grants-2006_09
Patent number
US07101884B2

Reaction notes

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