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Diethyl Ether → Benzyl 4-{(1R,2S)-2-[2-(2-tert-butoxy-2-oxoethyl-2,5-difluorophenoxy)ethyl]cyclopropyl}piperidine-1-carboxylate

HRID 1474714
ノート
印刷プレビュー

反応式

HRID 1474714 の反応式
Br[C:2]1[C:29]([F:30])=[CH:28][C:5]([O:6][CH2:7][CH2:8][C@@H:9]2[CH2:11][C@@H:10]2[CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])[CH2:14][CH2:13]2)=[C:4]([F:31])[CH:3]=1.[Cl-].[C:33]([O:37]C(=O)C[Zn+])([CH3:36])([CH3:35])[CH3:34].[CH2:42]([O:44]CC)[CH3:43].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1COCC1.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:33]([O:37][C:4]1([F:31])[C:3]([CH2:43][CH:42]=[O:44])=[CH:2][C:29]([F:30])=[CH:28][CH:5]1[O:6][CH2:7][CH2:8][C@@H:9]1[CH2:11][C@@H:10]1[CH:12]1[CH2:13][CH2:14][N:15]([C:18]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[O:19])[CH2:16][CH2:17]1)([CH3:36])([CH3:35])[CH3:34]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 3283Diethyl EtherHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 70818516Benzyl 4-{(1R,2S)-2-[2-(4-bromo-2,5 difluorophenoxy)ethyl]cyclopropyl}piperidine-1-carboxylateHCID 178451183HCID 178451183、化合物

生成物 1

HCID 117678479Benzyl 4-{(1R,2S)-2-[2-(2-tert-butoxy-2-oxoethyl-2,5-difluorophenoxy)ethyl]cyclopropyl}piperidine-1-carboxylate

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
65 °C

実験手順

Benzyl 4-{(1R,2S)-2-[2-(4-bromo-2,5 difluorophenoxy)ethyl]cyclopropyl}piperidine-1-carboxylate (0.540 g, 1.09 mmol) in THF (5 ml) was added 0.5 M 2-tert-butoxy-2-oxoethylzinc chloride in diethyl ether (5.46 ml, 2.73 mmol), followed by Pd2(dba)3 (50 mg, 0.055 mmol) and 52 mg X-Phos. The vessel was evacuated and back filled with nitrogen (3×) and the mixture was heated at 65° C. overnight. Saturated ammonium chloride (10 ml) was added and the mixture extracted with EtOAc (15 ml). The organic layer was separated, dried over Na2SO4, and concentrated. The residue was purified by column chromatography on silica gel (Biotage SNAP column, 25 g) using a gradient 0-15% then 15% EtOAc in hexanes to afford the title compound. LC/MS (m/z): 552.4 (M+Na)+.

後処理

  1. customThe vessel was evacuated
  2. additionback filled with nitrogen (3×)
  3. additionSaturated ammonium chloride (10 ml) was added
  4. extractionthe mixture extracted with EtOAc (15 ml)
  5. customThe organic layer was separated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (Biotage SNAP column, 25 g)

出典と根拠

ORDレコード
ord-4cddd796ddf846608004cbbd855633d5
出典データセット
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09018224B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート