Iodine → HCID 131713230, compound

HRID 1649396Notes

Reaction equation

HRID 1649396 reaction equation
[CH:1]1([C:6]([OH:8])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.O.ON1C2C=CC=CC=2N=N1.[NH2:20][CH:21]([P:30]([CH2:35][C:36]([N:38]1[CH2:49][CH2:48][CH2:47][C@H:39]1[C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])=[O:37])([O:32][CH2:33][CH3:34])=[O:31])[CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C.II>O1CCCC1.CN(C)C=O.CC(C)=O>[CH:1]1([C:6]([NH:20][CH:21]([P:30]([CH2:35][C:36]([N:38]2[CH2:49][CH2:48][CH2:47][C@H:39]2[C:40]([O:42][C:43]([CH3:44])([CH3:46])[CH3:45])=[O:41])=[O:37])([O:32][CH2:33][CH3:34])=[O:31])[CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

9

Reactant 5

HCID 807IodineHCID 8471TriethylamineHCID 18840Cyclopentanecarboxylic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 70480510HCID 70480510, compound

Product 1

HCID 131713230HCID 131713230, compound

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of cyclopentanecarboxylic acid (0.26 g., 0.0023 mole) and 1-hydroxybenzotriazole hydrate (0.31 g., 0.0023 mole) in tetrahydrofuran (10 ml.) is cooled to 0°, followed by the portionwise addition of N,N-dicyclohexylcarbodiimide (0.47 g., 0.0023 mole). The bath is removed and the mixture is stirred at ambient temperature for 70 minutes. After filtration, the mixture is concentrated in vacuo. To the residue, dissolved in dimethylformamide (8 ml.) plus tetrahydrofuran (10 ml.), is added a solution of (±)-1-[[[1-(amino)-3-phenylpropyl]ethoxyphosphinyl]acetyl]-L-proline, 1,1-dimethylethyl ester (1 g., 0.0023 mole), prepared for example as described in Example 85 (d), and triethylamine (0.25 g., 0.0025 mole) in dimethylformamide (10 ml.). The mixture is stirred at ambient temperature for 16 hours. It is then concentrated in vacuo and the residue is dissolved in ethyl acetate (75 ml.), washed with water, 10% citric acid, saturated sodium bicarbonate, brine, and dried (MgSO4). The solvent is removed in vacuo to give 1.2 g. of an amber oil residue. It is chromatographed on silica gel, eluted with dichloromethane, dichloromethane/acetone (4:1) to give 1.1 g. of (±)-1-[[[[1-(cyclopentylcarbonyl)amino]-3-phenylpropyl]ethoxyphosphinyl]acetyl]-L-proline, 1,1-dimethylethyl ester as an oil in two fractions: 0.8 g., Tlc, silica gel, acetone, shows a single spot at Rf 0.55; and 0.3 g., Tlc, shows two spots, Rf 0.55 and Rf 0.52 (visualized with PMA plus heat, or I2 vapor).

Workup

  1. customThe bath is removed
  2. filtrationAfter filtration
  3. concentrationthe mixture is concentrated in vacuo
  4. dissolutionTo the residue, dissolved in dimethylformamide (8 ml.)
  5. stirringThe mixture is stirred at ambient temperature for 16 hours
  6. concentrationIt is then concentrated in vacuo
  7. dissolutionthe residue is dissolved in ethyl acetate (75 ml.)
  8. washwashed with water, 10% citric acid, saturated sodium bicarbonate, brine
  9. dry with materialdried (MgSO4)
  10. customThe solvent is removed in vacuo
  11. customto give 1.2 g
  12. customIt is chromatographed on silica gel
  13. washeluted with dichloromethane, dichloromethane/acetone (4:1)
  14. customto give 1.1 g

Sources & evidence

ORD record
ord-7eee757d423a4f5ab1672222fd9e821d
Source dataset
uspto-grants-1983_11
Patent number
US04416831

Reaction notes

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