Diisobutylaluminum hydride → (E)-1-[2-[4-[3-[4-[3-(1-Pyrrolidinyl)-1-propenyl]benzyl]benzo[b]thiophen-2-yl]phenoxy]ethyl]pyrrolidine Dioxalate

HRID 1070329Notes

Reaction equation

HRID 1070329 reaction equation
[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[C:7]([OH:12])(=[O:11])[C:8]([OH:10])=[O:9].[N:13]1([CH2:18][C:19]#[C:20][C:21]2[CH:50]=[CH:49][C:24]([CH2:25][C:26]3[C:27]4[CH:48]=[CH:47][CH:46]=[CH:45][C:28]=4[S:29][C:30]=3[C:31]3[CH:44]=[CH:43][C:34]([O:35][CH2:36][CH2:37][N:38]4[CH2:42][CH2:41][CH2:40][CH2:39]4)=[CH:33][CH:32]=3)=[CH:23][CH:22]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1.CC(C[AlH]CC(C)C)C>C1(C)C=CC=CC=1>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[C:7]([OH:12])(=[O:11])[C:8]([OH:10])=[O:9].[N:13]1([CH2:18]/[CH:19]=[CH:20]/[C:21]2[CH:22]=[CH:23][C:24]([CH2:25][C:26]3[C:27]4[CH:48]=[CH:47][CH:46]=[CH:45][C:28]=4[S:29][C:30]=3[C:31]3[CH:44]=[CH:43][C:34]([O:35][CH2:36][CH2:37][N:38]4[CH2:39][CH2:40][CH2:41][CH2:42]4)=[CH:33][CH:32]=3)=[CH:49][CH:50]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 867570901-[2-[4-[3-[4-[3-(1-Pyrrolidinyl)-1-propynyl]benzyl]benzo[b]thiophen-2-yl]phenoxy]ethyl]pyrrolidine Dioxalate

Product 1

HCID 86757091(E)-1-[2-[4-[3-[4-[3-(1-Pyrrolidinyl)-1-propenyl]benzyl]benzo[b]thiophen-2-yl]phenoxy]ethyl]pyrrolidine DioxalateYield 439.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
40 °C

Procedure

A solution of 1-[2-(4-[3-[4-[3-(1-pyrrolidinyl)-1-propynyl]benzyl]benzo[b]thiophen-2-yl]phenoxy]ethyl]pyrrolidine (Example 129, Part D; 95 mg, 0.182 mmol) in 1.5 mL of toluene was treated with DIBAL-H (455 mL, 0.455 mmol; 1 M in toluene). The resulting mixture was heated at 40° C. for 3 h. The reaction mixture was cooled to 0° C. and quenched with excess MeOH. Saturated K+Na+ tartrate solution and EtOAc (10 mL each) were added, and the biphasic mixture was vigorously stirred for 2 h. The layers were separated, and the aqueous layer was extracted with EtOAc (10 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. Purification by radial chromatography (SiO2; 98:1.5:0.5 CHCl3—MeOH—NH4OH) afforded 42 mg (0.80 mmol, 44%) of a pale yellow oil which was converted to the dioxalate salt according to the methods detailed in Example 1, Part C.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. customquenched with excess MeOH
  3. additionSaturated K+Na+ tartrate solution and EtOAc (10 mL each) were added
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (10 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by radial chromatography (SiO2; 98:1.5:0.5 CHCl3—MeOH—NH4OH)

Sources & evidence

ORD record
ord-67bc5c31d5344098b8d62d0cf2be5520
Source dataset
uspto-grants-2001_06
Patent number
US06251921B1

Reaction notes

Loading…