Sodium Hydroxide → (2beta,3alpha,5alpha)-2-(2,2-Diethyl-4-morpholinyl)-3-hydroxypregnane-11,20-dione

HRID 233512ノート

反応式

HRID 233512 の反応式
Cl.[CH2:2]([C:4]1([CH2:10][CH3:11])[O:9][CH2:8][CH2:7][NH:6][CH2:5]1)[CH3:3].C(C1(CC)CO1)C.[OH:19][C@@H:20]1[C@@H:39](N2CCOC(C)(C)C2)[CH2:38][C@@:37]2([CH3:48])[C@@H:22]([CH2:23][CH2:24][C@@H:25]3[C@@H:36]2[C:35](=[O:49])[CH2:34][C@@:33]2([CH3:50])[C@H:26]3[CH2:27][CH2:28][C@@H:29]2[C:30](=[O:32])[CH3:31])[CH2:21]1.[OH-].[Na+]>C(O)CO.O>[CH2:2]([C:4]1([CH2:10][CH3:11])[O:9][CH2:8][CH2:7][N:6]([C@H:39]2[CH2:38][C@@:37]3([CH3:48])[C@@H:22]([CH2:23][CH2:24][C@@H:25]4[C@@H:36]3[C:35](=[O:49])[CH2:34][C@@:33]3([CH3:50])[C@H:26]4[CH2:27][CH2:28][C@@H:29]3[C:30](=[O:32])[CH3:31])[CH2:21][C@@H:20]2[OH:19])[CH2:5]1)[CH3:3]

参加物

7

反応物 4

HCID 14798Sodium HydroxideHCID 2959712,2-DiethyloxiraneHCID 9803583Org-21465HCID 233563652,2-Diethylmorpholine hydrochloride

生成物 1

HCID 10790676(2beta,3alpha,5alpha)-2-(2,2-Diethyl-4-morpholinyl)-3-hydroxypregnane-11,20-dione

試薬・触媒・溶媒 2

HCID 174Ethylene Glycol溶媒HCID 962Water溶媒

反応条件

温度
110 °C

実験手順

2,2-Diethylmorpholine hydrochloride (9.6 g) [prepared from the known 2,2-diethyloxirane (B. Rickborn et al, J. Am. Chem. Soc., 1971, 93, 1693) in a similar manner as for the preparation of 2,2-dimethylmorpholine of Example 1] was added to a stirred mixture (3.5:1) of (2α,3α,5α)-2,3-epoxypregnane-11,20-dione 20-cyclic 1,2-ethanediyl acetal and its 3α,4α-epoxy isomer (5.0 g) (prepared as described in British patent 1,039,441) in 1,2-ethanediol (50 ml). Powdered sodium hydroxide (2.14 g) was then added and the mixture was heated at 110° C. for 22 h and then poured into water (500 ml). The precipitated solid was filtered off, washed with water and suspended in a mixture of methanol (45 ml) and water (10 ml). Methanesulfonic acid (1.4 ml) was added and the resulting solution was stirred at room temperature for 45 min and then poured into water (500 ml). After extraction with ethyl acetate, aqueous sodium hydroxide (4M) was added to the aqueous phase until the pH exceeded 9. The precipitated solid was filtered off, washed with water and dissolved in dichloromethane. After washing the solution with water and drying over sodium sulfate, the solvent was removed under reduced pressure to afford an amorphous solid which was crystallised from diethyl ether to give (2β,3α,5α)-2-(2,2-diethyl-4-morpholinyl)-3-hydroxypregnane-11,20-dione (2.04 g). m.p. 177°-179° C.; [α]D +126.0° (c 0.7).

後処理

  1. filtrationThe precipitated solid was filtered off
  2. washwashed with water
  3. additionsuspended in a mixture of methanol (45 ml) and water (10 ml)
  4. additionMethanesulfonic acid (1.4 ml) was added
  5. additionpoured into water (500 ml)
  6. extractionAfter extraction with ethyl acetate, aqueous sodium hydroxide (4M)
  7. additionwas added to the aqueous phase until the pH
  8. filtrationThe precipitated solid was filtered off
  9. washwashed with water
  10. dissolutiondissolved in dichloromethane
  11. washAfter washing the solution with water
  12. dry with materialdrying over sodium sulfate
  13. customthe solvent was removed under reduced pressure
  14. customto afford an amorphous solid which
  15. customwas crystallised from diethyl ether

出典と根拠

ORDレコード
ord-5bc63dbe45d349209afbcb7711f57e41
出典データセット
uspto-grants-1997_01
特許番号
US05593983

反応ノート

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