Benzene, 1-bromo-3-(trifluoromethyl)- → N-((R)-1-(Naphthalen-1-yl)ethyl)-4-(3-(trifluoromethyl)phenyl)morpholine-3-carboxamide

HRID 1048855노트

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HRID 1048855 반응식
[C:1]1([C@H:11]([NH:13][C:14]([CH:16]2[CH2:21][O:20][CH2:19][CH2:18][NH:17]2)=[O:15])[CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.Br[C:65]1[CH:70]=[CH:69][CH:68]=[C:67]([C:71]([F:74])([F:73])[F:72])[CH:66]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(OCC)C.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[C:1]1([C@H:11]([NH:13][C:14]([CH:16]2[CH2:21][O:20][CH2:19][CH2:18][N:17]2[C:65]2[CH:70]=[CH:69][CH:68]=[C:67]([C:71]([F:74])([F:73])[F:72])[CH:66]=2)=[O:15])[CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

참가 물질

8

반응물 4

HCID 9817Benzene, 1-bromo-3-(trifluoromethyl)-HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 68293286N-((R)-1-(Naphthalen-1-yl)ethyl)morpholine-3-carboxamide

생성물 1

HCID 68293184N-((R)-1-(Naphthalen-1-yl)ethyl)-4-(3-(trifluoromethyl)phenyl)morpholine-3-carboxamide수율 33.3%

시약·촉매·용매 3

HCID 71406666Palladium--tri-tert-butylphosphane (1/1)촉매HCID 1140Toluene용매HCID 3283Diethyl Ether용매

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온도
110 °C

실험 절차

To a mixture solution of N-((R)-1-(naphthalen-1-yl)ethyl)morpholine-3-carboxamide (Intermediate-1) (400 mg, 1.4 mmol) in toluene (10 mL), bis(tri-tert-butylphosphine palladium(0) (19.3 mg, 0.021 mmol), xantphos (36.67 mg, 0.047 mmol), 1-bromo-3-(trifluoromethyl)benzene (244 μL, 1.69 mmol) and Cs2CO3 (688 mg, 2.11 mmol) were added. The reaction mass was heated to 110° C. and further maintained for 20 h under nitrogen atmosphere. After reaction completion the mixture was diluted with diethylether, filtered through celite, and concentrated under vacuum. The residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane as eluent to afford the title compound (200 mg), m/z 429.1.

후처리

  1. temperaturefurther maintained for 20 h under nitrogen atmosphere
  2. customAfter reaction completion the mixture
  3. filtrationfiltered through celite
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by column chromatography on silica gel using
  6. additiona mixture of ethyl acetate and hexane as eluent

출처 및 근거

ORD 기록
ord-55d8455482f24bab87b8ad851a7d425f
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382216B2

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