Cesium carbonate → (2S,3S)-1-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-[(1R)-1-(3-chloro-4-cyano-2-methylphenylamino)ethyl]pyrrolidine

HRID 501654ノート

反応式

HRID 501654 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@@H:9]1[C@H:21]([NH2:23])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:24][C:25]1[C:32]([CH3:33])=[C:31](I)[CH:30]=[CH:29][C:26]=1[C:27]#[N:28].C([O-])([O-])=O.[Cs+].[Cs+]>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].C[C@H](N(C)C)C1[CH-]C=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@@H:9]1[C@H:21]([NH:23][C:31]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25]([Cl:24])[C:32]=1[CH3:33])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 167319952-Chloro-4-iodo-3-methylbenzonitrileHCID 68457944(2S,3S)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-((1R)-1-aminoethyl)pyrrolidine

生成物 1

HCID 68459554(2S,3S)-1-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-[(1R)-1-(3-chloro-4-cyano-2-methylphenylamino)ethyl]pyrrolidine収率 18.2%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 44630263(S)-(R)-Ppfa触媒HCID 1140Toluene溶媒

反応条件

温度
140 °C

実験手順

To a solution of 80D (137 mg, 0.40 mmol) in nitrogen degassed toluene (3 mL) at rt was added 2-chloro-4-iodo-3-methyl-benzonitrile (122 mg, 0.44 mmol), Cs2CO3 (260 mg, 0.80 mmol) and Pd2(dba)3 (7.3 mg, 0.008 mmol) and (S)—N,N-dimethyl-1-[(R)-2-(diphenyphosphino)ferrocenyl]ethylamine (11 mg, 0.024 mmol). The reaction was degassed with nitrogen for 30 min, sealed and heated at 140° C. for 2 h under microwave conditions. The mixture was cool to rt, diluted with hexane and filtered through a layer of celite. The filtrate was evaporated to give the crude product. Purification by flash chromatography (10 g ISCO silica gel cartridge, 0-20% EtOAc in hexane gradient) gave the title compound 80E (36 mg): MS (ES) m/z 345 [M+H]+; HRMS calcd for C25H41N3O3ClSi 494.2606, found 494.2606.

後処理

  1. customThe reaction was degassed with nitrogen for 30 min
  2. customsealed
  3. temperatureThe mixture was cool to rt
  4. additiondiluted with hexane
  5. filtrationfiltered through a layer of celite
  6. customThe filtrate was evaporated
  7. customto give the crude product
  8. customPurification by flash chromatography (10 g ISCO silica gel cartridge, 0-20% EtOAc in hexane gradient)

出典と根拠

ORDレコード
ord-0e5e3028c98840dfb75095a0cd5c3dbc
出典データセット
uspto-grants-2010_08
特許番号
US07772267B2

反応ノート

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