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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
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HRID 2207660 반응식
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
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참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178419050
HCID 178419050, 화합물
촉매
HCID 962Water용매
HCID 6342Acetonitrile용매

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온도
100 °C

실험 절차

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;

후처리

  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%)

출처 및 근거

ORD 기록
ord-305f3995c6794fc0b81a71271f0d56f4
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09376436B2

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