Hydrochloric Acid → HCID 59807032, compound

HRID 1922456Notes

Reaction equation

HRID 1922456 reaction equation
P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.Br[C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH:24]1[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25]1)[CH2:19][CH2:18]2.[Li+].C[Si]([N-:35][Si](C)(C)C)(C)C.Cl.[OH-].[Na+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:29][N:26]1[CH2:27][CH2:28][CH:24]([N:20]2[C:21]3[C:17](=[CH:16][C:15]([NH2:35])=[CH:23][CH:22]=3)[CH2:18][CH2:19]2)[CH2:25]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2733832Lithium HexamethyldisilazideHCID 59807125HCID 59807125, compound

Product 1

HCID 59807032HCID 59807032, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
100 °C

Procedure

A suspension of Pd2(dba)3 (0.1 g, 0.113 mmol) and PtBu3 (1.38 mL, 0.455 mmol, 10% wt in hexane) in anhydrous THF (3 mL) was treated with a solution of compound 3 (0.64 g, 2.276 mmol) in THF (7 mL) followed by LiHMDS (4.55 mL, 4.552 mmol, 1 M solution in THF) at room temperature. The resulting dark brown mixture was heated to 100° C. and stirred for 3 hours in a sealed tube. The reaction mixture was cooled to room temperature and treated with 1 N HCl solution (5 mL) and stirred for 20 min. The reaction was basified with 2 N NaOH solution (25 mL) and product was extracted into CH2Cl2 (3×20 mL) and the combined organic fractions were washed with brine (20 mL) and dried (Na2SO4). The solvent was evaporated and crude product was purified by column chromatography on silica gel (2 N NH3 in MeOH:CH2Cl2, 5:95) to obtain compound 4 (0.44 g, 89%) as a syrup. 1H NMR (DMSO-d6) δ 6.38 (s, 1H), 6.30-6.23 (m, 2H), 4.31 (brs, 2H), 4.01-3.92 (m, 1H), 3.14 (t, 2H, J=8.1 Hz), 2.68 (t, 2H, J=8.1 Hz), 2.56-2.50 (m, 3H), 2.37-2.29 (m, 1H), 2.21 (s, 3H), 2.02-1.90 (m, 1H), 1.76-1.66 (m, 1H); ESI-MS (m/z, %): 218 (MH+, 100).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringstirred for 20 min
  3. extractionwas extracted into CH2Cl2 (3×20 mL)
  4. washthe combined organic fractions were washed with brine (20 mL)
  5. dry with materialdried (Na2SO4)
  6. customThe solvent was evaporated
  7. customcrude product was purified by column chromatography on silica gel (2 N NH3 in MeOH:CH2Cl2, 5:95)

Sources & evidence

ORD record
ord-8752562c7589448ca2abd4643a9e316d
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

Loading…