Cesium fluoride → tert-butyl ((5-(4-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)thiophen-2-yl)methyl)carbamate

HRID 1487436ノート

反応式

HRID 1487436 の反応式
Br[C:2]1[S:6][C:5]([CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][CH:3]=1.[Cl:16][CH:17]([Cl:36])[C:18]([NH:20][C@H:21]([CH2:34][F:35])[C@H:22]([OH:33])[C:23]1[CH:28]=[CH:27][C:26]([Sn](C)(C)C)=[CH:25][CH:24]=1)=[O:19].[F-].[Cs+]>C1(C)C=CC=CC=1.[Cu](I)I.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>[Cl:16][CH:17]([Cl:36])[C:18]([NH:20][C@H:21]([CH2:34][F:35])[C@@H:22]([C:23]1[CH:24]=[CH:25][C:26]([C:2]2[S:6][C:5]([CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][CH:3]=2)=[CH:27][CH:28]=1)[OH:33])=[O:19]

参加物

7

反応物 3

HCID 25953Cesium fluorideHCID 2779810tert-Butyl ((5-bromothiophen-2-yl)methyl)carbamateHCID 866953832,2-Dichloro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-trimethylstannanyl-phenyl)-ethyl]-acetamide

生成物 1

HCID 86695382tert-butyl ((5-(4-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)thiophen-2-yl)methyl)carbamate収率 63.1%

試薬・触媒・溶媒 3

HCID 83717Copper iodide触媒HCID 178418476HCID 178418476、化合物触媒HCID 1140Toluene溶媒

反応条件

温度
90 °C

実験手順

To a solution of tert-butyl ((5-bromothiophen-2-yl)methyl)carbamate (0.508 g, 1.74 mmol) and 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(trimethyl-stannyl)phenyl)propan-2-yl)acetamide (0.7 g, 1.58 mmol) in toluene (10 mL) is added cesium fluoride (0.478 g, 3.16 mmol) and copper iodide (30 mg, 0.158 mmol) and degassed with nitrogen for 30 minutes. To this mixture is added Pd(PPh3)2Cl2 (0.11 g, 0.16 mmol) and the mixture is heated to 90° C. for 26 hours. The solvent is evaporated in vacuo to get the crude which is purified by column chromatography on silica gel using methanol in CH2Cl2 to afford the title compound (490 mg): 1HNMR (400 MHz, DMSO-d6) δ:1.39 (s, 9H), 4.17-4.29 (m, 3.5H), 4.37-4.41 (m, 0.5H), 4.54-4.57 (m, 0.5H), 4.65-4.69 (m, 0.5H), 4.84 (t, J=3.56 Hz, 1H), 5.95 (d, J=4.12 Hz, 1H), 6.50 (s, 1H), 6.88 (d, J=3.48 Hz, 1H), 7.29-7.37 (dd, J=8.2 Hz, J=3.6 Hz, 3H), 7.51-7.56 (d, J=8.04 Hz, 3H). m/z (CI) 489[M−H].

後処理

  1. customdegassed with nitrogen for 30 minutes
  2. customThe solvent is evaporated in vacuo
  3. customto get the crude which
  4. customis purified by column chromatography on silica gel

出典と根拠

ORDレコード
ord-b7fae5a7e8eb4a1682b633b882b6fa99
出典データセット
uspto-grants-2016_08
特許番号
US09428528B2

反応ノート

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