Diisopropylamine → HCID 22496050, compound

HRID 1816006Notes

Reaction equation

HRID 1816006 reaction equation
[Li:1][CH2:2]CCC.[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[Li+].CC([N-]C(C)C)C.[Si:21]([O:28][CH:29]([C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)[C:30]#[N:31])([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].[CH2:38]([O:45][CH:46](Cl)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41]C=1>C1COCC1>[Li+:1].[CH3:7][CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])[CH3:8].[CH2:46]([O:45][C:38]1[CH:39]=[CH:44][C:43]([CH2:2][C:29]([O:28][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])([C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)[C:30]#[N:31])=[CH:42][CH:41]=1)[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 10634316HCID 10634316, compoundHCID 21972261HCID 21972261, compoundHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 22496050HCID 22496050, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

LDA was prepared by addition of n-BuLi (2.5 M in hexanes, 1.93 mL, 4.83 mmole) to a solution of diisopropylamine (0.63 mL, 4.83 mmole) in dry THF (5 mL) at 0° C. The LDA solution was added dropwise to a solution of 2-(tert-butyldimethylsilyloxy)-2-(pyridin-3-yl)acetonitrile (1.0 g, 4.03 mmole) in dry THF (15 mL) at −78° C. The solution was stirred for 15 min, then 1 benzyloxybenzyl chloride (1.41 g, 6.05 mmole) was added as a solid all at once. The reaction was kept at −78° C. for 15 min, then was warmed to RT. After 30 min at RT, the reaction was quenched with saturated aqueous NH4Cl and stirred for 20 min. EtOAc extraction (3×), drying (MgSO4), concentration, and flash chromatography on silica gel (20% EtOAc/hexanes) gave the title compound (769 mg, 43%) as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 8.80 (narrow m, 1 H), 8.67-8.70 (m, 1 H), 7.75-7.80 (m, 1 H), 7.33-7.53 (m, 6 H), 7.08 (d, 2 H), 6.93 (d, 2 H), 5.10 (s, 2 H), 3.30 (½ Abq, 1 H), 3.18 (½ Abq, 1 H), 0.99 (s, 9 H), 0.12 (s, 3H), 0.08 (s, 3H).

Workup

  1. waitThe reaction was kept at −78° C. for 15 min
  2. waitAfter 30 min at RT
  3. customthe reaction was quenched with saturated aqueous NH4Cl
  4. stirringstirred for 20 min
  5. extractionEtOAc extraction (3×)
  6. customdrying
  7. concentration(MgSO4), concentration, and flash chromatography on silica gel (20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-8fa3f127406d47ec96f0d6d09aabbe62
Source dataset
uspto-grants-2005_04
Patent number
US06881736B1

Reaction notes

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