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Methanol → Tert-butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(2-fluorophenyl)piperidine-1-carboxylate

HRID 391463
ノート
印刷プレビュー

反応式

HRID 391463 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[CH2:5][O:6][CH2:7][C:8]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[F:27])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.[C:35]([C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)#[N:36].[OH-].[K+].CO>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:35]([C:37]1[CH:42]=[CH:41][C:40]([C:2]2[CH:30]=[C:29]([C:31]([F:33])([F:34])[F:32])[CH:28]=[C:4]([CH2:5][O:6][CH2:7][C:8]3([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[F:27])[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:12][CH2:13]3)[CH:3]=2)=[CH:39][CH:38]=1)#[N:36]
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 887Methanol2 回HCID 14797Potassium HydroxideHCID 27343264-Cyanophenylboronic acidHCID 58993612Tert-butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(2-fluorophenyl)piperidine-1-carboxylate

生成物 1

HCID 58993685Tert-butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(2-fluorophenyl)piperidine-1-carboxylate

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
120 °C

実験手順

A sealable vial was charged with tert-butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(2-fluorophenyl)piperidine-1-carboxylate (0.138 g, 0.25 mmol) and 4-cyanophenylboronic acid (0.111 g, 0.75 mmol) in tetrahydrofuran (2 mL) at 0° C. To the reaction solution was added 1N potassium hydroxide (0.88 mL, 0.88 mmol) and Tetrakis(triphenylphosphine)palladium(0) (0.058 g, 0.05 mmol). The vial was purged with nitrogen and sealed. The sealed vial was heated in a microwave reactor at 120° C. for 2 hr. The reaction was cooled to room temperature and diluted with 4 mL ethyl acetate. The organic layer was separated, dried over Na2SO4 and evaporated in vacuo. The crude oil was purified by silica gel chromatography (5% ethyl acetate/95% hexanes→35% ethyl acetate/65% hexanes) to afford 0.123 g (87%) of the desired ether. Mass spec.: 591.22 (MNa)+; LC tr=4.318 min. (Phenomenex-Luna 4.6×50 mm S10, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA Gradient Time=4 min, Flow rate=4 mL/min).

後処理

  1. customThe vial was purged with nitrogen
  2. customsealed
  3. temperatureThe reaction was cooled to room temperature
  4. additiondiluted with 4 mL ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried over Na2SO4
  7. customevaporated in vacuo
  8. customThe crude oil was purified by silica gel chromatography (5% ethyl acetate/95% hexanes→35% ethyl acetate/65% hexanes)
  9. customto afford 0.123 g (87%) of the desired ether

出典と根拠

ORDレコード
ord-6971bf9477264b5d82c9fe80bef86847
出典データセット
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08383821B2

反応ノート

読み込み中…

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