Hexane → HCID 59807120, compound

HRID 1922490Notes

Reaction equation

HRID 1922490 reaction equation
C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CCCCCC.Br[C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[N:27]([CH2:31][CH2:32][N:33]([CH2:41][CH3:42])[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:26][CH2:25][CH2:24]2.C[Si]([N-:47][Si](C)(C)C)(C)C.[Li+].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>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]>[NH2:47][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[N:27]([CH2:31][CH2:32][N:33]([CH2:41][CH3:42])[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:26][CH2:25][CH2:24]2

Participants

8

Reactant 5

HCID 8058HexaneHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2724141Tetrabutylammonium FluorideHCID 2733832Lithium HexamethyldisilazideHCID 57343401HCID 57343401, compound2×

Product 1

HCID 59807120HCID 59807120, compoundYield 74.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of tris(dibenzylideneacetone)dipalladium(0) (66 mg, 0.072 mmol) in anhydrous THF (3 mL) was treated with tri-t-butylphosphine in hexane (10% wt) (0.435 mL, 0.143 mmol) and the mixture stirred for 5 minutes at room temperature. A solution of tert-butyl 2-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethyl(ethyl)carbamate (compound 5, 0.275 g, 0.717 mmol) in THF (7 mL) was added followed by Lithium bis(trimethylsilyl)amide (1M in THF, 1.435 mL, 1.435 mmol) and the mixture heated in a sealed reaction vial at 90° C. for 3 hours. The mixture was cooled to room temperature and treated with TBAF (1M in THF, 4 mL, 4 mmol) for 30 minutes. The mixture was partitioned between water (10 mL) and ethyl acetate (100 mL), transferred to a separatory funnel and the organic layer separated. The aqueous layer (pH=10) was further extracted with ethyl acetate and the combined organic layers washed with brine, dried over Na2SO4, filtered and concentrated to give a dark brown residue. Purification on silica gel eluting with 2.5% 2M NH3 in methanol/97.5% dichloromethane yielded a brown residue, 6 (171 mg, 74.6%). 1H-NMR ((DMSO-d6) δ 6.42 (d, 1H, J=8.5 Hz), 6.31-6.26 (m, 1H), 6.22 (br s, 1H), 4.20 (br s, 2H), 3.26-3.08 (m, 8H), 2.55 (t, 2H, J=6.3 Hz), 1.82-1.74 (m, 2H), 1.41 (s, 9H), 1.02 (t, 3H, J=7.0 Hz). MS (ESI+): 320 (MH+, 90), 264 (100).

Workup

  1. temperaturethe mixture heated in a sealed reaction vial at 90° C. for 3 hours
  2. temperatureThe mixture was cooled to room temperature
  3. customThe mixture was partitioned between water (10 mL) and ethyl acetate (100 mL)
  4. customtransferred to a separatory funnel
  5. customthe organic layer separated
  6. extractionThe aqueous layer (pH=10) was further extracted with ethyl acetate
  7. washthe combined organic layers washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a dark brown residue
  12. customPurification on silica gel eluting with 2.5% 2M NH3 in methanol/97.5% dichloromethane

Sources & evidence

ORD record
ord-8c84de0df75b40de878d7c4713033680
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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