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Sodium Carbonate → (2R,5S)-2-[4-(2-fluoro-5-hydroxy-phenyl)-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one

HRID 2207660
ノート
印刷プレビュー

反応式

HRID 2207660 の反応式
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C@H:8]2[CH2:12][CH2:11][C@@:10]3([CH2:16][CH2:15][N:14]([CH3:17])[C:13]3=[O:18])[NH:9]2)[CH:3]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][C:21]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>CC#N.O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][C:21]=1[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C@H:8]2[CH2:12][CH2:11][C@@:10]3([CH2:16][CH2:15][N:14]([CH3:17])[C:13]3=[O:18])[NH:9]2)[CH:3]=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 3

HCID 10340Sodium CarbonateHCID 467394012-Fluoro-5-hydroxyphenylboronic acidHCID 89649068(2R,5S)-2-(4-bromo-2-pyridyl)-7-methyl-1,7-diazaspiro[4.4]nonan-6-one

生成物 1

HCID 89649657(2R,5S)-2-[4-(2-fluoro-5-hydroxy-phenyl)-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one収率 77.9%

試薬・触媒・溶媒 3

HCID 178419050
HCID 178419050、化合物
触媒
HCID 962Water溶媒
HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

To a solution of (2R,5S)-2-(4-bromo-2-pyridyl)-7-methyl-1,7-diazaspiro[4.4]nonan-6-one (which may be prepared as described in Description 4) (140 mg, 0.4513 mmol) in MeCN (1.5 mL) and water (0.3000 mL) in a Smith microwave vessel was added (2-fluoro-5-hydroxy-phenyl)boronic acid (0.0774 g, 0.4965 mmol), bis(triphenylphosphine)palladium (II) dichloride (0.0095 g, 0.0135 mmol) and sodium carbonate (0.0957 g, 0.9027 mmol). The reaction vessel was sealed and purged with nitrogen. The reaction mixture was heated by microwave at 100° C. for 40 min. The reaction mixture was treated with water and was extracted with DCM twice and the organic layers were collected by passing down a PhaseSep cartridge. Evaporation of solvents gave an amber oil, It was further purified by silica gel chromatography (11 g KPNH silica cartridge) eluting with ethyl acetate in iso-hexane (20-100%) followed by methanol in ethyl acetate (0-18%) to give the desired product (2R,5S)-2-[4-(2-fluoro-5-hydroxy-phenyl)-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one (D134) (0.1200 g, 0.3515 mmol, 77.9% yield) as cream solid;

後処理

  1. customThe reaction vessel was sealed
  2. custompurged with nitrogen
  3. additionThe reaction mixture was treated with water
  4. extractionwas extracted with DCM twice
  5. customthe organic layers were collected
  6. customEvaporation of solvents
  7. customgave an amber oil, It
  8. customwas further purified by silica gel chromatography (11 g KPNH silica cartridge)
  9. washeluting with ethyl acetate in iso-hexane (20-100%)

出典と根拠

ORDレコード
ord-305f3995c6794fc0b81a71271f0d56f4
出典データセット
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09376436B2

反応ノート

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