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2-Fluoroethanol → 2-[4-[2-Fluoro-5-(2-fluoroethoxyl)phenyl]-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one

HRID 2207677
ノート
印刷プレビュー

反応式

HRID 2207677 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C@H:15]2[CH2:19][CH2:18][C@@:17]3([CH2:23][CH2:22][N:21]([CH3:24])[C:20]3=[O:25])[NH:16]2)[CH:10]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[F:61][CH2:62][CH2:63]O>C1COCC1.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:63][CH2:62][F:61])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([CH:15]2[CH2:19][CH2:18][C:17]3([CH2:23][CH2:22][N:21]([CH3:24])[C:20]3=[O:25])[NH:16]2)[CH:10]=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 97372-FluoroethanolHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 89649657(2R,5S)-2-[4-(2-fluoro-5-hydroxy-phenyl)-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one

生成物 1

HCID 1317359292-[4-[2-Fluoro-5-(2-fluoroethoxyl)phenyl]-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒
HCID 8028Tetrahydrofuran溶媒

反応条件

温度
120 °C

実験手順

To a Smith microwave vial was added (2R,5S)-2-[4-(2-fluoro-5-hydroxy-phenyl)-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one (which may be prepared as described in Description 134) (66.5 mg, 0.1900 mmol), triphenyl phosphine (102.19 mg, 0.3900 mmol), Di-tert-butyl azodicarboxylate ((89.71 mg, 0.3900 mmol) and 2-fluoroethanol (0.02 mL, 0.2900 mmol) in THF (0.5000 mL). Toluene (1 mL) was added. The reaction mixture was heated by microwave at 120° C. for 45 min. The reaction mixture was eluted on an SCX-2 cartrige (0.5 g) and washed with DCM followed MeOH. The desired product was eluted off the cartridge with ammonia in MeOH (0.2M). Evaporation of solvents gave colourless oil. The crude residue was purified by silica gel chromatography (KPNH silica 11 g) eluting with ethyl acetate in iso-hexane (10-100%) followed by methanol in ethyl acetate (0-18%). Evaporation of desired fractions gave colourless oil. It was further purified by a ChiralPak IA column eluting with ethanol/n-heptane (20%:80%) to give 2R,5S)-2-[4-[2-fluoro-5-(2-fluoroethoxyl)phenyl]-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;

後処理

  1. washThe reaction mixture was eluted on an SCX-2 cartrige (0.5 g)
  2. washwashed with DCM
  3. washThe desired product was eluted off the cartridge with ammonia in MeOH (0.2M)
  4. customEvaporation of solvents
  5. customgave colourless oil
  6. customThe crude residue was purified by silica gel chromatography (KPNH silica 11 g)
  7. washeluting with ethyl acetate in iso-hexane (10-100%)
  8. customEvaporation of desired fractions
  9. customgave colourless oil
  10. customIt was further purified by a ChiralPak IA column
  11. washeluting with ethanol/n-heptane (20%:80%)

出典と根拠

ORDレコード
ord-17edaf9f88644ef78aeec144ef89c9b8
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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