p-Toluenesulfonic acid → 5-(2-Oxohexahydrothieno[3,4-d]imidazol-6-yl)-pentanoic Acid 3-Iodopropyl Ester

HRID 217577

Reaction equation

HRID 217577 reaction equation
[OH:1][C:2]([CH2:4][CH2:5][CH2:6][CH2:7][C@H:8]1[C@@H:16]2[C@@H:11]([NH:12][C:13]([NH:15]2)=[O:14])[CH2:10][S:9]1)=[O:3].[I:17][CH2:18][CH2:19][CH2:20]O.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[I:17][CH2:18][CH2:19][CH2:20][O:3][C:2](=[O:1])[CH2:4][CH2:5][CH2:6][CH2:7][CH:8]1[CH:16]2[NH:15][C:13](=[O:14])[NH:12][CH:11]2[CH2:10][S:9]1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 693903-Iodo-1-propanolHCID 171548Biotin

Product 1

HCID 866412725-(2-Oxohexahydrothieno[3,4-d]imidazol-6-yl)-pentanoic Acid 3-Iodopropyl EsterYield 36.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of biotin (125 mg, 0.5 mmol), 3-iodo-1-propanol (150 μL, 1.6 mmol) and TsOH (10 mg, 0.05 mmol) in PhMe (50 mL)) was heated under reflux and Ar for 3 d in a Dean-Stark apparatus. After cooling down to ambient temperature, the mixture was filtered and the solvent distilled off under reduced pressure. The residue was dissolved in CH2Cl2 (30 mL) and washed with H2O (5 mL). The organic phase was dried (MgSO4) and concentrated under reduced pressure to yield 4 (75 mg, 36%) as a white solid. FABMS: m/z=413 [M+H]+; 1H-NMR (400 MHz, CDCl3): δ=1.40-1.45 (2H, m), 1.61-1.75 (4H, m), 2.10-2.16 (2H, m), 2.30 (2H, t, 7 Hz), 2.79 (1H, d, 13 Hz), 2.88 (1H, dd, 5 and 13 Hz), 3.15-3.18 (1H, m), 3.22 (2H, t, 7 Hz), 4.13 (2H, t, 6 Hz), 4.42-4.45 (1H, m), 4.61-4.65 (1H, m), 7.22 (1H, d, 8 Hz); 7.72 (1H, d, 8 Hz); 13C-NMR (100 MHz, CDCl3): δ=25.0, 28.4, 28.8, 32.6, 34.2, 40.5, 55.8, 61.8, 63.6, 64.4, 164.5, 173.9.

Workup

  1. temperatureunder reflux
  2. filtrationthe mixture was filtered
  3. distillationthe solvent distilled off under reduced pressure
  4. dissolutionThe residue was dissolved in CH2Cl2 (30 mL)
  5. washwashed with H2O (5 mL)
  6. dry with materialThe organic phase was dried (MgSO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e6b6d367fcd14702857bb6d468633735
Source dataset
uspto-grants-2012_06
Patent number
US08198099B2

Linked notes

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