Glycerol → 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid 2,3-dihydroxy-propyl ester

HRID 1827000Notes

Reaction equation

HRID 1827000 reaction equation
[OH:1][CH2:2][CH:3]([CH2:5][OH:6])[OH:4].[CH3:7][C:8]1[CH:12]=[C:11]([CH3:13])[NH:10][C:9]=1/[CH:14]=[C:15]1\[C:16](=[O:27])[N:17]([C:24](Cl)=[O:25])[C:18]2[C:23]\1=[CH:22][CH:21]=[CH:20][CH:19]=2>N1C=CC=CC=1.C1COCC1>[OH:4][CH:3]([CH2:5][OH:6])[CH2:2][O:1][C:24]([N:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)/[C:15](=[CH:14]/[C:9]2[NH:10][C:11]([CH3:13])=[CH:12][C:8]=2[CH3:7])/[C:16]1=[O:27])=[O:25]

Participants

5

Reactant 2

HCID 753GlycerolHCID 879046953-[1-(3,5-Dimethyl-1h-pyrrol-2-yl)-meth-(z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carbonyl chloride

Product 1

HCID 601112293-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid 2,3-dihydroxy-propyl ester

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To the solution of glycerol (460 mg, 2.5 mmol) in 1.0 mL of pyridine and 2.0 mL of THF was added a suspension of 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carbonyl chloride in 2.0 mL of THF at 0° C. The reaction mixture was gradually warmed to room temperature, stirred for 2.5 h, and concentrated. The residue was triturated with ethyl acetate and filtered. The solid was then washed with ethyl acetate, water, ether, and dried to yield 87 mg of 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid 2,3-dihydroxy-propyl ester. The combined filtrate was concentrated and partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated to give 120 mg of crude product which was suspended in water, filtered, and washed with small amount of ethyl acetate to afford another 67 mg of 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid 2,3-dihydroxy-propyl ester. The combined yield is 83%. 1H NMR (400 MHz, CDCl3) δ 12.51 (s, 1H, NH-1′), 7.90–7.92 (m, 1H), 7.45–7.48 (m, 1H), 7.37 (s, 1H, H-vinyl), 7.18–7.24 (m, 2H), 6.04 (d, J=1.96 Hz, 1H, H-4′), 4.68 (dd, J=3.13, 11.24 Hz, 1H, OCH2CH(OH)CH2OH), 4.45 (dd, J=4.89, 11.24 Hz, 1H, OCH2CH(OH)CH2OH), 4.09 (m, br, 1H, OCH2CH(OH)CH2OH), 3.86–3.99 (m, 2H, OCH2CH(OH)CH2OH), 3.60 (d, J=6.65 Hz, 1H, OCH2CH(OH)CH2OH), 3.45 (dd, J=5.52, 7.82 Hz, 1H, OCH2CH(OH)CH2OH), 2.41 (s, 3H, CH3), and 2.32 (s, 3H, CH3). MS m/z (relative intensity, %) 357 (100, [M+1]+.).

Workup

  1. concentrationconcentrated
  2. customThe residue was triturated with ethyl acetate
  3. filtrationfiltered
  4. washThe solid was then washed with ethyl acetate, water, ether
  5. customdried

Sources & evidence

ORD record
ord-db174b9013d34ecb835ea360118ba8f0
Source dataset
uspto-grants-2006_05
Patent number
US07053114B2

Reaction notes

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