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Dimethylformamide → Buprenorphine component OF alks-5461

HRID 881992
ノート
印刷プレビュー

反応式

HRID 881992 の反応式
[CH3:1][C@@:2]([OH:30])([C:26]([CH3:29])([CH3:28])[CH3:27])[C@@H:3]1[C@@:8]2([O:24][CH3:25])[C@@H:9]3[O:23][C:18]4=[C:19]([OH:22])[CH:20]=[CH:21][C:16]5=[C:17]4[C@:10]43[CH2:11][CH2:12][NH:13][C@H:14]([CH2:15]5)[C@@:5]4([CH2:6][CH2:7]2)[CH2:4]1.C(=O)(O)[O-].[Na+].[CH:36]1([CH2:39]Br)[CH2:38][CH2:37]1.CN(C=O)C>CO.O>[CH3:1][C@@:2]([OH:30])([C:26]([CH3:29])([CH3:28])[CH3:27])[C@@H:3]1[C@:8]2([O:24][CH3:25])[C@@H:9]3[O:23][C:18]4=[C:19]([OH:22])[CH:20]=[CH:21][C:16]5=[C:17]4[C@:10]43[CH2:11][CH2:12][N:13]([CH2:39][CH:36]3[CH2:38][CH2:37]3)[C@H:14]([CH2:15]5)[C@@:5]4([CH2:6][CH2:7]2)[CH2:4]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 6228Dimethylformamide2 回HCID 81503BromomethylcyclopropaneHCID 114976NorbuprenorphineHCID 516892Sodium Bicarbonate

生成物 1

HCID 9848990Buprenorphine component OF alks-5461収率 56.1%

試薬・触媒・溶媒 2

HCID 887
Methanol
溶媒
HCID 962Water溶媒2 回

反応条件

温度
90 °C

実験手順

A mixture of 11.5 g of norbuprenorphine, 4.6 g of sodium bicarbonate, 4.85 g of cyclopropylmethyl bromide (1% butenyl bromide in it by GC) and 46 ml of dry DMF is heated in an oilbath at 80-100° C. for 4 hours until the reaction is substantially complete. The reaction mixture is transferred to a dropping funnel, with minimal DMF as a wash. The reaction mixture is added over 5 minutes to 160 ml of water, with mechanical stirring. (Adding water to the reaction yields a gum). The mixture is stirred for about 10 minutes and filtered. The filter cake is washed with 20 ml water. The HPLC will show about 90% by area of desired product, and 0.2-0.5% of an N-butenyl substituted impurity. The resulting product is dried, yielding about 12 g. The resulting product is boiled in 30 ml of methanol for about 30 minutes, cooled, and filtered to yield about 7.3 g buprenorphine.

後処理

  1. customyields a gum)
  2. filtrationfiltered
  3. washThe filter cake is washed with 20 ml water
  4. customThe resulting product is dried
  5. customyielding about 12 g
  6. temperaturecooled
  7. filtrationfiltered

出典と根拠

ORDレコード
ord-665878874a614695aa8a58ab4b5d41f8
出典データセット
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08993764B2

反応ノート

読み込み中…

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