Methyl chloroglyoxylate → HCID 59408989, compound

HRID 1894732Notes

Reaction equation

HRID 1894732 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9]3=[C:10]([CH2:12][CH2:13][N:8]3[CH2:7][CH2:6][CH2:5]2)[CH:11]=1.C([Li])CCC.[Cu]C#N.Cl[C:23](=[O:28])[C:24]([O:26][CH3:27])=[O:25].C(=O)(O)[O-].[Na+]>O1CCCC1.ClCCl.O>[CH3:27][O:26][C:24](=[O:25])[C:23](=[O:28])[C:2]1[CH:3]=[C:4]2[C:9]3=[C:10]([CH2:12][CH2:13][N:8]3[CH2:7][CH2:6][CH2:5]2)[CH:11]=1

Participants

9

Reactant 5

HCID 79846Methyl chloroglyoxylateHCID 516892Sodium BicarbonateHCID 59409002HCID 59409002, compoundHCID 178418339ButyllithiumHCID 178418546HCID 178418546, compound

Product 1

HCID 59408989HCID 59408989, compoundYield 85.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution 8-bromo-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinoline (9.53 g, 40.0 mmol) in anhydrous tetrahydrofuran (317 ml) cooled to −78° C. was treated with n-butyllithium (36.1 ml, 90.1 mmol; 2.5M solution in hexanes) then stirred for 20 minutes. The reaction was treated with copper (I) cyanide (10.88 g, 120.1 mmol) then allowed to warm to between 0 and 10° C. before cooling back to −78° C. Methyl chlorooxoacetate (11.1 ml, 120.7 mmol) was added and the mixture was allowed to warm to room temperature. Water (250 ml) was added to the reaction and then the reaction was basified with saturated aqueous sodium bicarbonate. Dichloromethane (200 ml) was added and the mixture was filtered through a bed of celite. The organic layer was removed and the aqueous layer was extracted with dichloromethane (2×200 ml). The combined organic layers were dried with anhydrous sodium sulfate and evaporated to dryness to give a dark green oil which was purified by flash column chromatography (SiO2, 20% EtOAc in hexanes to 25% EtOAc in hexanes) to afford oxo-(1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-8-yl)-acetic acid methyl ester as a yellow/brown solid (8.4 g). M.p=102-105° C.; 400 MHz 1H NMR (CDCl3) δ: 7.55 (s, 1H), 7.50 (s, 1H), 3.92 (s, 3H), 3.58 (t, 2H), 3.19 (m, 2H), 3.01 (t, 2H), 2.66 (t, 2H), 2.02 (m, 2H); LCMS: 246 [M+H].

Workup

  1. temperatureto warm to between 0 and 10° C.
  2. temperatureto warm to room temperature
  3. filtrationthe mixture was filtered through a bed of celite
  4. customThe organic layer was removed
  5. extractionthe aqueous layer was extracted with dichloromethane (2×200 ml)
  6. dry with materialThe combined organic layers were dried with anhydrous sodium sulfate
  7. customevaporated to dryness
  8. customto give a dark green oil which
  9. customwas purified by flash column chromatography (SiO2, 20% EtOAc in hexanes to 25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-7c44f1b7012849e989c7acb3dde27691
Source dataset
uspto-grants-2013_08
Patent number
US08513292B2

Reaction notes

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