Trifluoroacetic acid → 6-Benzyloxy-3-[(3-methoxy-4-hydroxyphenyl)methyl]-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophene

HRID 1387107ノート

反応式

HRID 1387107 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:10]([C:12]2[C:13]3[CH:34]=[CH:33][C:32]([O:35][CH2:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)=[CH:31][C:14]=3[S:15][C:16]=2[C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:19][CH:18]=2)=O)[CH:6]=[CH:7][C:8]=1[OH:9].CC(C[AlH]CC(C)C)C.[SiH](CC)(CC)CC.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C1COCC1>[CH2:36]([O:35][C:32]1[CH:33]=[CH:34][C:13]2[C:12]([CH2:10][C:5]3[CH:6]=[CH:7][C:8]([OH:9])=[C:3]([O:2][CH3:1])[CH:4]=3)=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]4[CH2:27][CH2:28][CH2:29][CH2:30]4)=[CH:19][CH:18]=3)[S:15][C:14]=2[CH:31]=1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

参加物

7

反応物 5

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 14487Diisobutylaluminum hydrideHCID 516892Sodium BicarbonateHCID 183184716-Benzyloxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl 3-Methoxy-4-hydroxyphenyl Ketone

生成物 1

HCID 183184826-Benzyloxy-3-[(3-methoxy-4-hydroxyphenyl)methyl]-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophene

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A 0° C. solution of 6-benzyloxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl 3-methoxy-4-hydroxyphenyl ketone (Part D; 3.85 g, 6.64 mmol) in 100 mL of anhydrous THF was treated with DIBAL-H (17 mL, 1M solution in toluene) dropwise via syringe. After 1 hr at 0° C., the remaining DIBAL-H was quenched with excess MeOH. 100 mL of saturated Na+K+ tartrate and 50 mL of EtOAc were added, and the biphasic mixture was vigorously stirred for 1.5 hr at ambient temperature. The layers were separated, and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were dried over K2CO3, filtered and concentrated in vacuo. The crude residue was dissolved in 100 mL of 1,2-dichloroethane, and Et3SiH (9.4 mL, 58.7 mmol) was added. Upon cooling to 0° C., TFA (6.5 mL, 83.8 mmol) was added in a dropwise fashion. After 1.5 hr, the reaction mixture was poured into 300 mL of saturated NaHCO3 solution. The aqueous phase was extracted with EtOAc (2×150 mL). The combined organic layers were dried over K2CO3, filtered and concentrated in vacuo. Purification by PrepLC (SiO2; gradient of 0.5% to 2% MeOH in CHCl3, saturated with NH4OH) afforded 3.1 g (5.48 mmol; 83%) of a white solid.

後処理

  1. customthe remaining DIBAL-H was quenched with excess MeOH
  2. addition100 mL of saturated Na+K+ tartrate and 50 mL of EtOAc were added
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  5. dry with materialThe combined organic layers were dried over K2CO3
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe crude residue was dissolved in 100 mL of 1,2-dichloroethane
  9. temperatureUpon cooling to 0° C.
  10. waitAfter 1.5 hr
  11. extractionThe aqueous phase was extracted with EtOAc (2×150 mL)
  12. dry with materialThe combined organic layers were dried over K2CO3
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customPurification by PrepLC (SiO2; gradient of 0.5% to 2% MeOH in CHCl3, saturated with NH4OH)
  16. customafforded 3.1 g (5.48 mmol; 83%) of a white solid

出典と根拠

ORDレコード
ord-96b1fcfefecc49b1b9417ab5f981d924
出典データセット
uspto-grants-2001_07
特許番号
US06265575B1

反応ノート

読み込み中…