Triethylamine → tert-butyl [(1S)-2-(4-{[5-(cyclopropylmethoxy)pyridin-2-yl]ethynyl}phenoxy)-1-methylethyl]carbamate

HRID 1026316ノート

反応式

HRID 1026316 の反応式
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]([C:12]#[CH:13])=[N:10][CH:11]=2)[CH2:3][CH2:2]1.I[C:15]1[CH:32]=[CH:31][C:18]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH3:22])=[CH:17][CH:16]=1.C(N(CC)CC)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CN(C=O)C>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]([C:12]#[C:13][C:15]3[CH:32]=[CH:31][C:18]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[CH3:22])=[CH:17][CH:16]=3)=[N:10][CH:11]=2)[CH2:2][CH2:3]1

参加物

7

反応物 3

HCID 8471TriethylamineHCID 580470405-(Cyclopropylmethoxy)-2-ethynylpyridineHCID 86666304tert-butyl [(1S)-2-(4-iodophenoxy)-1-methylethyl]carbamate

生成物 1

HCID 86666303tert-butyl [(1S)-2-(4-{[5-(cyclopropylmethoxy)pyridin-2-yl]ethynyl}phenoxy)-1-methylethyl]carbamate収率 97.1%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

A mixture of 5-(cyclopropylmethoxy)-2-ethynylpyridine (591 mg), tert-butyl [(1S)-2-(4-iodophenoxy)-1-methylethyl]carbamate (1.67 g), bis(triphenylphosphine)palladium(II) dichloride (120 mg), copper(I) iodide (32.5 mg), triethylamine (518 mg) and DMF (10 mL) was stirred at 60° C. overnight under an argon atmosphere. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate and water, filtered through celite, and the aqueous layer was separated from the organic layer. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound as a yellow solid (1.40 g).

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with ethyl acetate and water
  3. filtrationfiltered through celite
  4. customthe aqueous layer was separated from the organic layer
  5. extractionThe separated aqueous layer was extracted again with ethyl acetate
  6. washThe combined organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

出典と根拠

ORDレコード
ord-d64dd34a15b9438b84c5f76deaecb5e4
出典データセット
uspto-grants-2014_05
特許番号
US08729102B2

反応ノート

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