Methyl chloroglyoxylate → N-[(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-2-oxo-ethyl]oxalamic acid methyl ester

HRID 644056Notes

Reaction equation

HRID 644056 reaction equation
[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19](=[O:22])[C:20]#[N:21])=[CH:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:23][O:24][C:25](=[O:29])[C:26](Cl)=[O:27].C(N(C(C)C)C(C)C)C>C(O)(=O)C.[Pd].ClCCl>[CH3:23][O:24][C:25](=[O:29])[C:26]([NH:21][CH2:20][C:19]([C:10]1[C:11]2[C:16](=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][CH:12]=2)[N:8]([CH2:7][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH:9]=1)=[O:22])=[O:27]

Participants

7

Reactant 3

HCID 79846Methyl chloroglyoxylateHCID 81531DiisopropylethylamineHCID 86613200(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-oxoacetonitrile

Product 1

HCID 68693889N-[(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-2-oxo-ethyl]oxalamic acid methyl esterYield 45%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-oxoacetonitrile (975 mg, 3.29 mmol) in acetic acid (40 ml) under nitrogen was added 10% palladium on charcoal (90 mg). The reaction was placed under a hydrogen atmosphere and stirred for 14 h. The reaction mixture was then filtered through a pad of dicalite. The dicalite was washed with acetic acid and the combined filtrate evaporated to leave a red oil. The red oil was taken up in dichloromethane (50 ml) and to this was added methylchlorooxoacetate (0.393 ml, 4.28 mmol) followed by N-ethyldiisopropylamine (1.7 ml, 9.87 mmol) dropwise. The reaction was stirred for 1 h and poured into a separating funnel. The organics were washed sequentially with 2M aqueous hydrochloric acid (50 ml), 5% aqueous sodium carbonate (50 ml) and brine (50 ml). The organics were dried over sodium sulfate, filtered and the solvent removed in vacuo to leave a brown oil. The oil was purified by flash chromatography using dichloromethane followed by 66% (v/v) diethyl ether in heptane to afford N-[(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-2-oxo-ethyl]oxalamic acid methyl ester (573 mg, 1.48 mmol) as a yellow/brown solid.

Workup

  1. filtrationThe reaction mixture was then filtered through a pad of dicalite
  2. washThe dicalite was washed with acetic acid
  3. customthe combined filtrate evaporated
  4. customto leave a red oil
  5. stirringThe reaction was stirred for 1 h
  6. additionpoured into a separating funnel
  7. washThe organics were washed sequentially with 2M aqueous hydrochloric acid (50 ml), 5% aqueous sodium carbonate (50 ml) and brine (50 ml)
  8. dry with materialThe organics were dried over sodium sulfate
  9. filtrationfiltered
  10. customthe solvent removed in vacuo
  11. customto leave a brown oil
  12. customThe oil was purified by flash chromatography

Sources & evidence

ORD record
ord-8846ec145140470abcdd709850acc87d
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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