Water → HCID 67975659, compound

HRID 1844087Notes

Reaction equation

HRID 1844087 reaction equation
Br[C:2]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:3]=1[CH2:4][CH:5]1[CH2:9][C:8](=[O:10])[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]12.O.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.C[CH2:39][N:40](CC)CC>CN(C=O)C.CN(C1C=CN=CC=1)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[C-]#N.[Zn+2]>[C:39]([C:2]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:3]=1[CH2:4][CH:5]1[CH2:9][C:8](=[O:10])[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]12)#[N:40]

Participants

9

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 67989352HCID 67989352, compound

Product 1

HCID 67975659HCID 67975659, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl 5-bromo-2-oxo-3,3a,4,8b-tetrahydroindeno[1,2-b]pyrrole-1-carboxylate F9 (1.5 g, 4.25 mmol) in DMF (30 mL) was added Pd(PPh3)4 (751 mg, 0.63 mmol) and Zn(CN)2 (1.00 g, 8.51 mmol). The solution was stirred at 100° C. for 16 h. After cooling, water was added and the solution was extracted with ethyl acetate. The organic layer was washed with brine three times, dried and concentrated. The crude material was dissolved in 50 ml acetonitrile in which were added Boc2O (5.5 g, 25.2 mmol), NEt3 (6 ml), and DMAP (520 mg, 4.26 mmol). The resulting mixture was stirred for 16 h. The dark brown solution was concentrated under vacuum, and the residue was dissolved in ethyl acetate. The organic layer was washed twice with HCl (1N), brine, dried and concentrated under vacuum. The residue was purified by flash chromatography eluting with ethyl acetate and cyclohexane (10/90 to 30/70 over 30 min.) to give 880 mg of the desired compound F11 as a beige gum (69%). LCMS (method E): 0.87 min; ES+: 619 [2M+Na].

Workup

  1. temperatureAfter cooling
  2. extractionthe solution was extracted with ethyl acetate
  3. washThe organic layer was washed with brine three times
  4. customdried
  5. concentrationconcentrated
  6. dissolutionThe crude material was dissolved in 50 ml acetonitrile in which
  7. stirringThe resulting mixture was stirred for 16 h
  8. concentrationThe dark brown solution was concentrated under vacuum
  9. dissolutionthe residue was dissolved in ethyl acetate
  10. washThe organic layer was washed twice with HCl (1N), brine
  11. customdried
  12. concentrationconcentrated under vacuum
  13. customThe residue was purified by flash chromatography
  14. washeluting with ethyl acetate and cyclohexane (10/90 to 30/70 over 30 min.)

Sources & evidence

ORD record
ord-b4eee2b292524c68a0ef4d1659f716b0
Source dataset
uspto-grants-2015_02
Patent number
US08946280B2

Reaction notes

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