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1-Bromo-4-(trifluoromethoxy)benzene → 1-(Tert-butoxycarbonyl)-4-[[4-(trifluoromethoxy)phenyl]amino]piperidine

HRID 511103
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HRID 511103 반응식
CC(C)([O-])C.[Na+].Br[C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([NH2:32])[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([NH:32][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]
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참가 물질

8

반응물 3

HCID 5210081-Bromo-4-(trifluoromethoxy)benzeneHCID 12682914-Amino-1-Boc-piperidineHCID 23676156Sodium t-butoxide

생성물 1

HCID 66237091-(Tert-butoxycarbonyl)-4-[[4-(trifluoromethoxy)phenyl]amino]piperidine수율 64.7%

시약·촉매·용매 4

HCID 634876Binap, (A+-)-촉매
HCID 9811564
Bis(dibenzylideneacetone)palladium
촉매
HCID 1140Toluene용매
HCID 8857Ethyl Acetate용매

실험 절차

Tris(dibenzylideneacetone)dipalladium (30 mg; 0.03 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (62 mg; 0.1 mmol), sodium tert-butoxide (240 mg; 2.5 mmol), 1-bromo-4-trifluoromethoxy-benzene (410 mg; 1.7 mmol) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (421 mg; 2.1 mmol) are suspended in dry toluene (5 mL) and the mixture is irradiated in a mono-mode microwave oven for 30 minutes at 120° C. The mixture is then cooled down to room temperature, is diluted with ethyl acetate (15 mL), filtered over Celite and concentrated under reduced pressure. The crude residue is then diluted in dichloromethane (15 mL) and filtered over a short silica gel pad. The desired product is eluted from the silica gel pad (dichloromethane (150 mL) followed by dichloromethane:methanol 98:2 (100 mL)). The fractions of interest are collected, pooled and concentrated under reduced pressure to afford the desired product (396 mg; 1.1 mmol).

후처리

  1. customthe mixture is irradiated in a mono-mode microwave oven for 30 minutes at 120° C
  2. filtrationfiltered over Celite
  3. concentrationconcentrated under reduced pressure
  4. additionThe crude residue is then diluted in dichloromethane (15 mL)
  5. filtrationfiltered over a short silica gel pad
  6. washThe desired product is eluted from the silica gel pad (dichloromethane (150 mL) followed by dichloromethane:methanol 98:2 (100 mL))
  7. customThe fractions of interest are collected
  8. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-f5fb15e956b5417593a7a9f8ee985fac
출처 데이터셋
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09096524B2

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