Hydrochloric Acid → (2beta,3alpha,5alpha)-21-Chloro-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)pregnane-11,20-dione

HRID 233494Notes

Reaction equation

HRID 233494 reaction equation
ClN1C(=[O:7])CCC1=O.[OH:9][C@@H:10]1[C@@H:32]([N:33]2[CH2:38][CH2:37][O:36][C:35]([CH3:40])([CH3:39])[CH2:34]2)[CH2:31][C@@:30]2([CH3:41])[C@@H:12]([CH2:13][CH2:14][C@@H:15]3[C@@H:29]2[C:28](=[O:42])[CH2:27][C@@:26]2([CH3:43])[C@H:16]3[CH2:17][CH2:18][C@@H:19]2[C:20](=NCCO)[CH3:21])[CH2:11]1.[ClH:44].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.O>[Cl:44][CH2:21][C:20](=[O:7])[C@@H:19]1[C@:26]2([CH3:43])[C@H:16]([C@H:15]3[C@H:29]([C:28](=[O:42])[CH2:27]2)[C@:30]2([CH3:41])[C@H:12]([CH2:11][C@H:10]([OH:9])[C@@H:32]([N:33]4[CH2:38][CH2:37][O:36][C:35]([CH3:39])([CH3:40])[CH2:34]4)[CH2:31]2)[CH2:13][CH2:14]3)[CH2:17][CH2:18]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 31398ChlorosuccinimideHCID 86750168(2beta,3alpha,5alpha)-3-Hydroxy-20-[(2-hydroxyethyl)imino]-2-(2,2-dimethyl-4-morpholinyl)pregnan-11-one

Product 1

HCID 10672358(2beta,3alpha,5alpha)-21-Chloro-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)pregnane-11,20-dione

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-Chlorosuccinimide (2.16 g) was added to a solution of (2β,3α,5α)-3-hydroxy-20-[(2-hydroxyethyl)imino]-2-(2,2-dimethyl-4-morpholinyl)pregnan-11-one (8.77 g) in tetrahydrofuran (175 ml). The solution was stirred at room temperature for 2 h and hydrochloric acid (53 ml; 1M) was then added. After stirring at room temperature for 1.25 h, the reaction mixture was poured into water (1 l). The pH was adjusted to 9 with aqueous sodium carbonate and the precipitated solid was filtered off, washed with water and dissolved in dichloromethane. After drying over sodium sulfate, the solvent was removed under reduced pressure and the residue was chromatographed on silica gel. The purified product was crystallised from diethyl ether to give (2β,3α,5α)-21-chloro-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)pregnane-11,20-dione (3.23 g). m.p. 206°-208° C. (dec); [α]D +130.5° (c 0.57).

Workup

  1. stirringAfter stirring at room temperature for 1.25 h
  2. filtrationthe precipitated solid was filtered off
  3. washwashed with water
  4. dissolutiondissolved in dichloromethane
  5. dry with materialAfter drying over sodium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customthe residue was chromatographed on silica gel
  8. customThe purified product was crystallised from diethyl ether

Sources & evidence

ORD record
ord-b045a551b7044123b5b4f767142570fa
Source dataset
uspto-grants-1997_01
Patent number
US05593983

Reaction notes

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