Tetrahydrofuran → HCID 86616983, compound

HRID 2426791Notes

Reaction equation

HRID 2426791 reaction equation
[C:1]1([C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:8][C@H:9]([C:11]([O:13][CH3:14])=[O:12])[CH3:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1.Cl.[N:37]1[CH:42]=[CH:41][C:40]([CH2:43]Cl)=[CH:39][CH:38]=1>CN(C=O)C>[C:1]1([C:7](=[N:8][C:9]([CH3:10])([CH2:43][C:40]2[CH:41]=[CH:42][N:37]=[CH:38][CH:39]=2)[C:11]([O:13][CH3:14])=[O:12])[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 745704-(Chloromethyl)pyridinium chlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 11119053HCID 11119053, compound

Product 1

HCID 86616983HCID 86616983, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of methyl N-(diphenylmethylene)alaninate from Step A (9.78 g, 36.6 mmol) in 60 ml DMF at 0° C. was added a 1M solution of sodium bis(trimethylsilyl)amide in THF (45.72 ml, 45.72 mmol) over a 20 min period. After 30 min, a solution of 4-picolyl chloride hydrochloride (3.00 g, 18.29 mmol) in 40 ml DMF was added to the reaction via cannula over a 25 min period. The reaction was warmed to rt and stirred for 5 h. The reaction was quenched with saturated aqueous NH4Cl and extracted with EtOAc (3×). The combined organic layers were washed with 3M LiCl (2×) and brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by silica gel chromatography (0-40% EtOAc/hexanes) afforded methyl 2-[(diphenylmethylene)amino]-2-methyl-3-pyridin-4-ylpropanoate as a white solid (5.28 g, 81%). LCMS [M+H]=359.2. 1H NMR (d4-MeOH) δ 8.51 (dd, J=4.5, 1.5 Hz, 2H), 7.56 (dd, J=8.4, 1.4 Hz, 2H), 7.40-7.37 (m, 4H), 7.34-7.30 (m, 2H), 7.26-7.23 (m, 2H), 7.10-7.07 (m, 2H), 3.33 (A of AB, d, J=13.0 Hz, 1H), 3.27 (s, 3H), 3.18 (B of AB, d, J=12.9 Hz, 1H), 1.32 (s, 3H).

Workup

  1. customThe reaction was quenched with saturated aqueous NH4Cl
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organic layers were washed with 3M LiCl (2×) and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by silica gel chromatography (0-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-844bbfd136c540d38f047bc125977392
Source dataset
uspto-grants-2011_06
Patent number
US07968571B2

Reaction notes

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