Dichloromethane → HCID 86754199, compound

HRID 581715Notes

Reaction equation

HRID 581715 reaction equation
[NH2:1][C@@:2]12[C@H:19]3[C@@H:10]([C@:11]4([CH3:21])[C@H:16]([CH2:17][CH2:18]3)[CH2:15][C@@H:14]([OH:20])[CH2:13][CH2:12]4)[CH2:9][CH2:8][C@:6]1([CH3:7])[C@@H:5]([C:22]([O:24][CH3:25])=[O:23])[CH2:4][CH2:3]2.[C:26](N1C=CN=C1)(N1C=CN=C1)=[O:27].[C:38]1([C@@H:44]([CH2:46][OH:47])[NH2:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(Cl)[Cl:49]>>[ClH:49].[NH2:1][C@@:2]12[C@H:19]3[C@@H:10]([C@:11]4([CH3:21])[C@H:16]([CH2:17][CH2:18]3)[CH2:15][C@@H:14]([O:20][C:26]([NH:45][CH:44]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH2:46][OH:47])=[O:27])[CH2:13][CH2:12]4)[CH2:9][CH2:8][C@:6]1([CH3:7])[C@@H:5]([C:22]([O:24][CH3:25])=[O:23])[CH2:4][CH2:3]2

Participants

5

Reactant 4

HCID 6344Dichloromethane2×HCID 682631,1'-CarbonyldiimidazoleHCID 1347972-Amino-2-phenylethan-1-olHCID 15863846HCID 15863846, compound

Product 1

HCID 86754199HCID 86754199, compound

Procedure

To a solution of 1.4 g (0.004 mole) of (3β,5β,14β,17β)-14-Amino-3-hydroxyandrostane-17-carboxylic Acid, Methyl Ester, prepared according to the procedure described in U.S. Pat. No. 4,885,280, incorporated by reference herein, in 50 ml of CH2Cl2 under N2 and stirring, is added 0.72 g (0.0044 mole) of 1,1'-carbonyldiimidazole. After 2 days 2.74 g (0.02 mole) of S-2-phenylglycinol is dissolved in a minimum amount of CH2Cl2 and is added to the reaction mixture. The reaction mixture is heated at reflux for 4 days and another 0.54 g (0.004 mole) of (S)-2-phenylglycinol is added. The mixture is heated further at reflux temperature for 6 days. The solution is concentrated at reduced pressure and the residue is taken up with fresh CH2Cl2, is washed well with H2O until the washing is neutral. After drying over MgSO4, CH2Cl2 is removed under reduced pressure to yield the crude free base. The solid is purified by flash chromatography (5% MeOH/CH2Cl2, NH4OH) and then converted to its hydrochloride salt by the treatment with ethanolic HCl. Two crops of (3β(S),5β,14β,17β)-14-Amino-3-[[[(2-hydroxy-1-phenylethyl)amino]carbonyl]oxy]androstane-17-carboxylic Acid, Methyl Ester Hydrochloride Final Product are obtained.

Workup

  1. additionis added to the reaction mixture
  2. temperatureThe reaction mixture is heated
  3. temperatureat reflux for 4 days
  4. temperatureThe mixture is heated further
  5. temperatureat reflux temperature for 6 days
  6. concentrationThe solution is concentrated at reduced pressure
  7. washis washed well with H2O until the washing
  8. dry with materialAfter drying over MgSO4, CH2Cl2
  9. customis removed under reduced pressure
  10. customto yield the crude free base
  11. customThe solid is purified by flash chromatography (5% MeOH/CH2Cl2, NH4OH)

Sources & evidence

ORD record
ord-42a57cbe3ed649899c9470e413ee4e82
Source dataset
uspto-grants-1999_07
Patent number
US05922703

Reaction notes

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