Hydrochloric Acid → (R)-2-[4-(4-Thiophen-3-yl-phenoxy)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 750069ノート

反応式

HRID 750069 の反応式
[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=2)=[CH:2]1.[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@@H:21]1[CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30](I)=[CH:29][CH:28]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)CC(O)=O.Cl>O1CCOCC1.[Cu]I>[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@@H:21]1[CH2:25][O:26][C:27]1[CH:28]=[CH:29][C:30]([O:12][C:9]2[CH:10]=[CH:11][C:6]([C:3]3[CH:4]=[CH:5][S:1][CH:2]=3)=[CH:7][CH:8]=2)=[CH:31][CH:32]=1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 41303424-(Thiophen-3-yl)phenolHCID 44819166(R)-2-(4-Iodo-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 69000335(R)-2-[4-(4-Thiophen-3-yl-phenoxy)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester収率 70.9%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
98 °C

実験手順

To a 25 mL pressure resistant vial which contained a solution of the product from step 1 (44 mg, 0.25 mmol) and the product from step 2 (130 mg, 0.33 mmol) in anhydrous dioxane (4 mL) were added cesium carbonate (300 mg, 1.5 mmol) and N,N-dimethylglycine.HCl (25 mg, 0.66 mmol) at rt. The reaction mixture was flushed with argon and copper (I) iodide (14 mg, 0.06 mmol) was added. The vial was sealed and the reaction mixture was stirred at 98° C. for 72 h. After cooling to rt, the mixture was poured onto 50 mL ice-water solution and this solution was extracted with EtOAc (3×20 mL). The combined organic layers were washed with water (2×20 mL), brine (20 mL) and dried over anhydrous Na2SO4. The solvent was removed in vacuo to obtain the crude product which was purified by silica gel flash chromatography to afford the title product (80 mg, 70%); LCMS; 100%, APCI+ Calcd: 451.6. found m/z: 451.6 (M); 1H NMR (400 MHz, CDCl3); δ 1.48 (s, 9H), 1.81-2.09 (m, 4H), 3.27-3.48 (m, 2H), 3.70-3.97 (m, 1H), 4.02-4.21 (m, 2H), 6.88-7.05. (m, 6H), 7.32-7.38 (m, 3H), 7.52 (d, J=8.8 Hz, 2H):

後処理

  1. customat rt
  2. additionwas added
  3. customThe vial was sealed
  4. temperatureAfter cooling to rt
  5. extractionthis solution was extracted with EtOAc (3×20 mL)
  6. washThe combined organic layers were washed with water (2×20 mL), brine (20 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. customThe solvent was removed in vacuo
  9. customto obtain the crude product which
  10. customwas purified by silica gel flash chromatography

出典と根拠

ORDレコード
ord-3971664528684e77baea048c7a747da3
出典データセット
uspto-grants-2008_07
特許番号
US07402684B2

反応ノート

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