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

HRID 1048855ノート

反応式

HRID 1048855 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 71406666Palladium--tri-tert-butylphosphane (1/1)触媒HCID 1140Toluene溶媒HCID 3283Diethyl Ether溶媒

反応条件

温度
110 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-55d8455482f24bab87b8ad851a7d425f
出典データセット
uspto-grants-2016_07
特許番号
US09382216B2

反応ノート

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