Citric Acid → HCID 9971472, compound

HRID 1613621Notes

Reaction equation

HRID 1613621 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20](OCC)=[O:21])[CH:18]=2)[NH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C.CO.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([CH2:20][OH:21])[CH:18]=2)[NH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 887MethanolHCID 10042391AGN-PC-0MXS0FHCID 21225700Diisobutylaluminumhydride2×

Product 1

HCID 9971472HCID 9971472, compoundYield 90.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-50 °C

Procedure

To a cooled (-50° C.) and stirred solution of the product from Step 3 (17.4 g, 52.4 mmol) in anhydrous tetrahydrofuran (650 ml) was added dropwise via cannula diisobutylaluminium hydride (1M in toluene; 168 ml) over 23 minutes, under a nitrogen atmosphere. After being stirred at -25° C. for 1 hour, additional diisobutylaluminium hydride (1M in toluene; 40 ml) was added dropwise over 15 minutes and stirring was continued at -25° C. for further 30 minutes. Methanol (65 ml) was added dropwise (CAUTION! H2 evolution) at -35° C. followed by aqueous citric acid (10%; 450 ml) and the organic phase was decanted off. The aqueous solution was extracted with ethyl acetate (500 ml) and the combined organic phases were washed with brine (1×200 ml), dried (Na2SO4) and concentrated. Flash chromatography (silica gel, dichloromethane-methanol, 97:3) of the remaining residue gave 13.8 g (90.8%) of the title compound as a white solid. A sample recrystallised from dichloromethane showed: mp 129°-130° C.; δH (360 MHz, DMSO-d6) 10.70 (1H, br s, indole N--H), 7.44 (1H, s, Ar--H), 7.26 (1H, d, J=8.3 Hz, Ar--H), 7.10 (1H, s, Ar--H), 7.03 (1H, d, J=8.3 Hz, Ar--H), 6.86 (1H, br t, --NH--), 4.95 (1H, t, J=5.6 Hz, --OH), 4.54 (2H, d, J=5.6 Hz, --CH2OH), 3.18 (2H, m, --CH2N--), 2.78 (2H, t, J=7.2 Hz, --CH2 --), 1.38 (9H, s, t-Bu); m/z (EI) 290 (M+). (Found: C, 65.95; H, 7.82; N, 9.37. C16H22N2O3 requires: C, 66.18; H, 7.64; N, 9.65%).

Workup

  1. stirringstirring
  2. waitwas continued at -25° C. for further 30 minutes
  3. customthe organic phase was decanted off
  4. extractionThe aqueous solution was extracted with ethyl acetate (500 ml)
  5. washthe combined organic phases were washed with brine (1×200 ml)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3be29cddf05c4079a066b60724aa98e1
Source dataset
uspto-grants-1993_03
Patent number
US05194440

Reaction notes

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