Propargyl alcohol → HCID 12083033, compound

HRID 1168508Notes

Reaction equation

HRID 1168508 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([Li])CCC.Br[C:26]1[CH:27]=[C:28]2[C:33]3=[C:34]([CH2:36][C:37]([CH3:39])([CH3:38])[N:32]3[CH:31]=[C:30]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[C:29]2=[O:45])[CH:35]=1.[CH2:46]([OH:49])[C:47]#[CH:48]>C1COCC1.C(NCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Cu](I)I>[OH:49][CH2:46][C:47]#[C:48][C:26]1[CH:27]=[C:28]2[C:33]3=[C:34]([CH2:36][C:37]([CH3:39])([CH3:38])[N:32]3[CH:31]=[C:30]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[C:29]2=[O:45])[CH:35]=1

Participants

9

Reactant 4

HCID 7859Propargyl alcoholHCID 11776TriphenylphosphineHCID 12083032ethyl 8-bromo-2,2-dimethyl-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxylateHCID 178418339Butyllithium

Product 1

HCID 12083033HCID 12083033, compound

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 167845palladium(II) acetateCatalystHCID 8021DiethylamineSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22 °C

Procedure

A solution of palladium acetate (73 mg) and triphenyl phosphine (191 mg) in dry THF (6.0 mL) under nitrogen is cooled to 0° C. A solution of n-butyllithium (1.6 M in hexanes, 444 μL) is added dropwise and after 15 min, the solution is warmed to 22° C. for 15 min. The solution is then canulated into a mixture of ethyl 8-bromo-2,2-dimethyl-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxylate (Preparation 13, 350 mg), copper iodide (84 mg) and propargyl alcohol (75 μL) in diethylamine (6.0 mL). The reaction is warmed to 45° C. for 2 hours. The reaction is filtered, diluted with CH2Cl2 (100 mL), and washed with water. The organic layer is dried (MgSO4), filtered, and concentrated. The crude product is chromatographed over silica gel, eluting with 5% MeOH in CHCl3 and recrystallized from EtOAc to afford 229 mg of the title compound as white crystals. Physical characteristics: M.p. 237° C. (dec); 1H NMR (DMSO-d6) δ8.74, 7.81, 7.60, 5.37, 4.33, 4.23, 3.39, 1.63 (s, 6 H), 1.29 (t, J=7 Hz, 3 H); IR (diffuse reflectance) 2391, 2222, 2058, 1921, 1680, 1637, 1595, 1542, 1510, 1317, 1216, 1186, 1040, 1031, 808 cm−1; MS (EI) m/z 325 (M+). HRMS (FAB) m/z 326.1385 (C19H19NO4+H).

Workup

  1. temperatureThe reaction is warmed to 45° C. for 2 hours
  2. filtrationThe reaction is filtered
  3. additiondiluted with CH2Cl2 (100 mL)
  4. washwashed with water
  5. dry with materialThe organic layer is dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is chromatographed over silica gel
  9. washeluting with 5% MeOH in CHCl3
  10. customrecrystallized from EtOAc

Sources & evidence

ORD record
ord-0e66815af6544d0cb65813a957abd6a8
Source dataset
uspto-grants-2003_09
Patent number
US06624159B2

Reaction notes

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