Tributylamine → tert-butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy)phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate

HRID 2054749

反応式

HRID 2054749 の反応式
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([CH:8]2[CH:12]=[CH:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9]2)[CH:7]=1.[C:21]([Si:25]([O:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31](I)[CH:30]=1)([CH3:27])[CH3:26])([CH3:24])([CH3:23])[CH3:22].C(N(CCCC)CCCC)CCC.C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Si:25]([O:28][C:29]1[CH:34]=[C:33]([CH:11]2[CH:12]=[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[F:20])[CH2:9][N:10]2[C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH:32]=[CH:31][CH:30]=1)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:27])[CH3:26]

参加物

7

反応物 4

HCID 7622TributylamineHCID 11773TriphenylarsineHCID 27572803-(t-Butyldimethylsiloxy)iodobenzeneHCID 59656601tert-butyl 3-(5-chloro-2-fluorophenyl)-2,3-dihydro-1H-pyrrole-1-carboxylate

生成物 1

HCID 59682334tert-butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy)phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
65 °C

実験手順

A deoxygenated mixture of tert-butyl 3-(5-chloro-2-fluorophenyl)-2,3dihydro-1H-pyrrole-1-carboxylate (3-1, 1.100 g, 3.69 mmol, 1 equiv), tert-butyl(3-iodophenoxy)dimethylsilane (1.85 g, 5.54 mmol, 1.50 equiv), tributylamine (1.76 mL, 7.39 mmol, 2.00 equiv), triphenylarsine (0.453 g, 1.48 mmol, 0.400 equiv), and palladium acetate (0.166 g, 0.739 mmol, 0.200 equiv) in DMF (10 mL) was heated at 65° C. for 20 h. The reaction mixture was partitioned between water (100 mL) and ethyl acetate (2×85 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (100% hexanes initially, grading to 50% ethyl acetate in hexanes) to provide tert-butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-4(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate (3-2) as an orange oil. 1H NMR (300 MHz, CDCl3) major rotamer: δ 7.11-6.53 (m, 7H), 6.11 (s, 1H), 5.32 (m, 1H), 4.53 (m, 2H), 1.09 (s, 9H), 0.79 (s, 9H), 0.00 (s, 6H). LRMS m/z (M+H) 504.1 found, 504.2 required.

後処理

  1. customThe reaction mixture was partitioned between water (100 mL) and ethyl acetate (2×85 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography (100% hexanes initially

出典と根拠

ORDレコード
ord-b184480e084541b9908f3929904a0a10
出典データセット
uspto-grants-2008_02
特許番号
US07329762B2

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