Hydrochloric Acid → HCID 10528790, compound

HRID 36592Notes

Reaction equation

HRID 36592 reaction equation
[OH:1][C@@H:2]1[C@@H:21]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH2:20][C@@:19]2([CH3:28])[C@@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:18]2[CH2:17][CH2:16][C@@:15]2([CH3:29])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C:12](=[O:14])[CH3:13])[CH2:3]1.Cl.C(Cl)(=O)C.[Br:35]Br.C(=O)([O-])[O-].[Na+].[Na+]>CO.O>[Br:35][CH2:13][C:12](=[O:14])[C@@H:11]1[C@:15]2([CH3:29])[C@H:8]([C@H:7]3[C@H:18]([CH2:17][CH2:16]2)[C@:19]2([CH3:28])[C@H:4]([CH2:3][C@H:2]([OH:1])[C@@H:21]([N:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)[CH2:20]2)[CH2:5][CH2:6]3)[CH2:9][CH2:10]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 10340Sodium CarbonateHCID 24408BromineHCID 120616Pregnan-20-one, 3-hydroxy-2-(4-morpholinyl)-, (2beta,3alpha,5alpha)-

Product 1

HCID 10528790HCID 10528790, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

To a stirred suspension of 100 g of (2β,3α,5α)-3-hydroxy-2-(4-morpholinyl)pregnan-20-one, prepared according to British Patent 1,039,441, in 2.5 l of methanol were added 81 ml of 3M methanolic hydrogen chloride and 10 ml of acetyl chloride. Bromine (16.6 ml) in 1 l of methanol was added dropwise over 1.5 h. The mixture was stirred at room temperature for a further 20 min and then poured into 18 l of water. Aqueous sodium carbonate solution was added until the pH exceeded 9.0 and the precipitated solid was filtered, washed with water and dissolved in dichloromethane. The solution was dried over sodium sulfate, the solvent removed, and the residue crystallized from acetone-hexane to give 46 g of (2β,3α,5α)-21-bromo-3-hydroxy-2-(4-morpholinyl)pregnan-20-one. 5.0 g of this 21-bromo compound were dissolved in 50 ml of 1-methyl-2-pyrrolidinone and 2.5 g of lithium chloride were added. The mixture was stirred at 80° C. under nitrogen for 2 h, cooled to room temperature and poured into 500 ml of water. The precipitated solid was filtered off, washed with water and dissolved in dichloromethane. The solution was dried over sodium sulfate, the solvent removed, and the residue crystallized from acetone-hexane to give 2 g of (2β,3α,5α)-21-chloro-3-hydroxy-2-(4-morpholinyl)pregnan-20-one as in Example 1.

Workup

  1. customprepared
  2. filtrationthe precipitated solid was filtered
  3. washwashed with water
  4. dissolutiondissolved in dichloromethane
  5. dry with materialThe solution was dried over sodium sulfate
  6. customthe solvent removed
  7. customthe residue crystallized from acetone-hexane

Sources & evidence

ORD record
ord-6dfe6252cbec486e8835f1fa7bfa46f8
Source dataset
uspto-grants-1995_05
Patent number
US05416079

Reaction notes

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