Nitrogen → ST069377

HRID 2065999노트

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HRID 2065999 반응식
[F:1][C:2]1[CH:19]=[CH:18][C:5]([C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][C:9]=2[CH2:16][OH:17])=[O:7])=[CH:4][CH:3]=1.N#N.C(OC(B)OC(C)C)(C)C>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]([OH:7])[C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][C:9]=2[CH2:16][OH:17])=[CH:18][CH:19]=1

참가 물질

5

반응물 3

HCID 947NitrogenHCID 109450024-(4-Fluorobenzoyl)-3-(hydroxymethyl)benzonitrileHCID 178419211HCID 178419211, 화합물

생성물 1

HCID 9921362ST069377수율 10%

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
-80 °C

실험 절차

145 mg of 4-(4-fluorobenzoyl)-3-hydroxymethyl-benzonitrile (0.56 mmol, 1.0 eq.) and 100 mg of 1S,2R—N-methylephedrine 99% (0.56 mmol, 1.0 eq.) are dissolved in a two-necked round bottomed flask in 3 mL of toluene under an inert atmosphere (N2). At room temperature, 160 μL of diisopropoxymethyl borane (0.59 mmol, 1.05 eq.) is added. The reaction mixture is brought to 70° C. and stirred at this temperature for 30 minutes. The solvent is gently removed under reduced pressure within 15 minutes. 3 mL of toluene is added and the reaction mixture is cooled to −80° C. 800 μL (2 eq.) of a 1.3M solution of dimethylaminopropyl magnesium chloride in THF is slowly added (duration: 2 minutes). Stirring is continued for 10 minutes at −80° C. HPLC control indicated a conversion of >90%. The ratio of S-diol (4-[(S)-4-dimethylamino-1-(4-fluorophenyl)-1-hydroxy-butyl]-3-hydroxymethyl-benzonitrile) to R-diol (4-[(R)-4-dimethylamino-1-(4-fluorophenyl)-1-hydroxy-butyl]-3-hydroxymethyl-benzonitrile) is 71.6:28.4 (enantiomeric excess=43.2%). About 10% of 4-[(4-fluorophenyl)-hydroxy-methyl]-3-hydroxymethyl-benzonitrile are formed as a byproduct.

후처리

  1. customis brought to 70° C.
  2. customThe solvent is gently removed under reduced pressure within 15 minutes
  3. addition3 mL of toluene is added
  4. addition800 μL (2 eq.) of a 1.3M solution of dimethylaminopropyl magnesium chloride in THF is slowly added (duration: 2 minutes)
  5. stirringStirring
  6. waitis continued for 10 minutes at −80° C

출처 및 근거

ORD 기록
ord-f08624d5c0c2404682682fdce0f6060e
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288569B2

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