Ammonia → (R)-5-(5-Bromo-2-fluoro-phenyl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

HRID 1946914ノート

反応式

HRID 1946914 の反応式
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:16])=[C:6]([C@@:8]2([CH3:15])[NH:13][C:12](=S)[CH2:11][O:10][CH2:9]2)[CH:7]=1.[NH3:17].C(OO)(C)(C)C>CO.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:16])=[C:6]([C@:8]2([CH3:15])[CH2:9][O:10][CH2:11][C:12]([NH2:17])=[N:13]2)[CH:7]=1

参加物

6

反応物 3

HCID 222AmmoniaHCID 6410tert-Butyl hydroperoxideHCID 86668499(R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholine-3-thione

生成物 1

HCID 58155238(R)-5-(5-Bromo-2-fluoro-phenyl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

試薬・触媒・溶媒 2

HCID 887Methanol溶媒2 回HCID 962Water溶媒

実験手順

A pressure tube was charged with a solution of (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholine-3-thione (1.93 g, 6.3 mmol) in methanol (195 ml). A solution of ammonia in methanol (7M, 54 ml, 381 mmol) and an aqueous solution of tert-butyl hydroperoxide (70%, 8.17 g, 63.4 mmol) were added. The tube was sealed and the reaction mixture was stirred overnight at room temperature for 21 hours. For the workup, the reaction mixture was diluted with water and extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulphate and evaporated. The crude product was purified by chromatography on an Isolute flash NH2 column using dichloromethane as the eluent. The (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine was obtained as an off-white gum (1.42 g, 62% of theory). MS (ISP): m/z=287.1 [M+H]+, 289.0 [M+2+H]+.

後処理

  1. customThe tube was sealed
  2. extractionextracted three times with dichloromethane
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulphate
  5. customevaporated
  6. customThe crude product was purified by chromatography on an Isolute flash NH2 column

出典と根拠

ORDレコード
ord-5c4afc2b2ed64f9faa1aee23992df241
出典データセット
uspto-grants-2013_03
特許番号
US08399459B2

反応ノート

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