Hexane → HCID 59807040, compound

HRID 1922493Notes

Reaction equation

HRID 1922493 reaction equation
C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CCCCCC.[C:20]([O:24][C:25](=[O:43])[N:26]([CH2:30][CH2:31][N:32]1[C:41]2[C:36](=[CH:37][C:38](Br)=[CH:39][CH:40]=2)[CH2:35][CH2:34][CH2:33]1)[CH:27]([CH3:29])[CH3:28])([CH3:23])([CH3:22])[CH3:21].C[Si]([N-:48][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]>[C:20]([O:24][C:25](=[O:43])[N:26]([CH2:30][CH2:31][N:32]1[C:41]2[C:36](=[CH:37][C:38]([NH2:48])=[CH:39][CH:40]=2)[CH2:35][CH2:34][CH2:33]1)[CH:27]([CH3:29])[CH3:28])([CH3:23])([CH3:22])[CH3:21]

Participants

8

Reactant 5

HCID 8058HexaneHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2724141Tetrabutylammonium FluorideHCID 2733832Lithium HexamethyldisilazideHCID 57343399HCID 57343399, compound2×

Product 1

HCID 59807040HCID 59807040, compoundYield 67.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of tris(dibenzylideneacetone)dipalladium(0) (35 mg, 0.038 mmol in anhydrous THF (3 mL) was treated with tri-t-butylphosphine in hexane (10% wt) (0.229 mL, 0.076 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(isopropyl)carbamate (compound 3, 0.150 g, 0.378 mmol) in THF (7 mL) was added followed by lithium bis(trimethylsilyl)amide (1M in THF, 0.755 mL, 0.755 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, 3 mL, 3 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-red residue. Purification on silica gel eluting with 2.5% 2M NH3 in methanol/97.5% dichloromethane yielded a dark brown residue, 4 (85 mg, 67.5%). 1H-NMR (DMSO-d6) δ 6.44 (d, 1H, J=8.0 Hz), 6.28 (dd, 1H, J=8.3, 2.1 Hz), 6.24-6.18 (m, 1H), 4.33-3.91 (br m+br s, 3H), 3.24-3.04 (m, 6H), 2.60-2.50 (m, 2H), 1.85-1.74 (m, 2H), 1.44 (s, 9H), 1.07 (d, 6H, J=6.8 Hz). MS (ESI+): 334 (MH+, 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-red residue
  12. customPurification on silica gel eluting with 2.5% 2M NH3 in methanol/97.5% dichloromethane

Sources & evidence

ORD record
ord-5d43d28d303b4c6794f45b3da4398769
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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