Tetrabutylammonium Fluoride → HCID 67383703、化合物

HRID 335856ノート

反応式

HRID 335856 の反応式
[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([C:19]3[C:14](=[N:15][CH:16]=[C:17](Br)[CH:18]=3)[O:13][C:12]3[C:7]2=[CH:8][C:9]([OH:21])=[CH:10][CH:11]=3)[N:6]=1.C[Si](C)(C)[C:24]#[C:25][C:26]1([CH3:30])[CH2:29][O:28][CH2:27]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:24]#[C:25][C:26]4([CH3:30])[CH2:29][O:28][CH2:27]4)[CH:18]=3)[O:13][C:12]3[C:7]2=[CH:8][C:9]([OH:21])=[CH:10][CH:11]=3)[N:6]=1

参加物

7

反応物 3

HCID 2724141Tetrabutylammonium FluorideHCID 58466114(S)-2'-amino-3-bromo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-olHCID 58547788Trimethyl((3-methyloxetan-3-yl)ethynyl)silane

生成物 1

HCID 67383703HCID 67383703、化合物

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
70 °C

実験手順

A sealable tube was charged with (S)-2′-amino-3-bromo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol (3.00 g, 8.62 mmol), tetrakis(triphenylphosphine)palladium (0.996 g, 0.862 mmol), copper(i) iodide (0.164 g, 0.862 mmol). To this was added trimethyl((3-methyloxetan-3-yl)ethynyl)silane (2.90 g, 17.23 mmol) followed by tetra-n-butylammonium fluoride (1 M in THF) (25.9 mL, 25.9 mmol). The resulting brown solution was flushed with argon and heated at 70° C. for 5 hours. The reaction was cooled to rt and diluted with 250 mL of water. The slurry was poured into a separatory funnel containing EtOAc (500 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3×250 mL). In the first extraction a slight emulsion formed, this was cleared upon the addition of 50 mL of brine. The aqueous layer was then extracted with CH2Cl2 (3×200 mL). The organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown foam that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (330 g), 0-100% CH2Cl2 to 10:1 methanol in methylenechloride with 0.1% ammonium hydroxide) to provide (S)-2′-amino-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol as a brown foam.

後処理

  1. customThe resulting brown solution was flushed with argon
  2. temperatureThe reaction was cooled to rt
  3. additiondiluted with 250 mL of water
  4. additionThe slurry was poured into a separatory funnel
  5. additioncontaining EtOAc (500 mL)
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with EtOAc (3×250 mL)
  8. extractionIn the first extraction a slight emulsion
  9. customformed
  10. extractionThe aqueous layer was then extracted with CH2Cl2 (3×200 mL)
  11. washThe organic layers were washed with brine
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customto provide a brown foam that
  16. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (330 g), 0-100% CH2Cl2 to 10:1 methanol in methylenechloride with 0.1% ammonium hydroxide)

出典と根拠

ORDレコード
ord-9b7e7004b8eb4f30838097d4624cb6c7
出典データセット
uspto-grants-2014_11
特許番号
US08883782B2

反応ノート

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