Cesium carbonate → Methyl 2-((S)-6-((R)-4-(2,6-dimethyl-4-(3-(methylsulfonyl)propoxy)phenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

HRID 237510

反応式

HRID 237510 の反応式
Br[C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C@H:6]2[O:12][C:13]1[CH:26]=[CH:25][C:16]2[C@H:17]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH2:18][O:19][C:15]=2[CH:14]=1.[CH3:27][C:28]1[CH:33]=[C:32]([O:34][CH2:35][CH2:36][CH2:37][S:38]([CH3:41])(=[O:40])=[O:39])[CH:31]=[C:30]([CH3:42])[C:29]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:42][C:30]1[CH:31]=[C:32]([O:34][CH2:35][CH2:36][CH2:37][S:38]([CH3:41])(=[O:39])=[O:40])[CH:33]=[C:28]([CH3:27])[C:29]=1[C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C@H:6]2[O:12][C:13]1[CH:26]=[CH:25][C:16]2[C@H:17]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH2:18][O:19][C:15]=2[CH:14]=1

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 86697103{(S)-6-[(R)-4-bromo-7-fluoro-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester2 回HCID 866971722-(2,6-Dimethyl-4-(3-(methylsulfonyl)propoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

生成物 1

HCID 86697171Methyl 2-((S)-6-((R)-4-(2,6-dimethyl-4-(3-(methylsulfonyl)propoxy)phenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate収率 20.3%

試薬・触媒・溶媒 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 1140Toluene溶媒

反応条件

温度
120 °C

実験手順

Methyl 2-((S)-6-((R)-4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate [intermediate 1, step 3] (32 mg), 2-(2,6-dimethyl-4-(3-(methylsulfonyl)propoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (42 mg), [1,1′-bis(diphenylphosphino)-ferrocene]-dichloropalladium-(II) (6 mg), 1,1′-bis(diphenylphosphino)-ferrocene (4 mg) and caesium carbonate (50 mg) are suspended in toluene (2 mL) and degassed for 5 minutes with a flow of nitrogen. The mixture is heated under microwave irradiation for 90 minutes at 120° C. The mixture is diluted with ethyl acetate, washed with water, the organic phase dried and the solvent removed under vacuum. The residue is purified by chromatography on silica gel (cyclohexane/ethyl acetate 100:0→50:50) to give the title compound (9 mg). LC (method 19): tR=1.38 min; Mass spectrum: m/z=583 [M+H]+.

後処理

  1. customdegassed for 5 minutes with a flow of nitrogen
  2. additionThe mixture is diluted with ethyl acetate
  3. washwashed with water
  4. customthe organic phase dried
  5. customthe solvent removed under vacuum
  6. customThe residue is purified by chromatography on silica gel (cyclohexane/ethyl acetate 100:0→50:50)

出典と根拠

ORDレコード
ord-77fc04c6f6774be492d87f6c4292db09
出典データセット
uspto-grants-2014_02
特許番号
US08642585B2

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