HCID 59161318, compound → HCID 59161248, compound

HRID 545538Notes

Reaction equation

HRID 545538 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH2:9][CH2:8][C@@H:7]([NH:15][C:16](=[O:20])[CH:17]([CH3:19])[CH3:18])[CH2:6][C:5]2=1.[Cu][C:22]#[N:23]>CN1CCCC1=O.O.CCOC(C)=O.C(N)CN.[Cu]I.[Cu]>[C:22]([C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH2:9][CH2:8][C@@H:7]([NH:15][C:16](=[O:20])[CH:17]([CH3:19])[CH3:18])[CH2:6][C:5]2=1)#[N:23]

Participants

9

Reactant 2

HCID 59161318HCID 59161318, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 59161248HCID 59161248, compoundYield 63.2%

Reagents, catalysts & solvents 6

HCID 23978CopperCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 3301EthylenediamineSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

Dissolve (R)-N-(6-bromo-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isobutyramide (Preparation 21) (1.00 g, 2.98 mmol) in 1-methyl-2-pyrolidinone (30 mL). Sparge the resulting solution with nitrogen for 15 min. Add copper(I) cyanide (801 mg, 8.95 mmol) and copper(I) iodide (1.70 g, 8.95 mmol). Heat to 130° C. for three days, then cool to room temperature. Dilute the reaction mixture with water (100 mL), EtOAc (250 mL), and enough ethylene diamine to dissolve the copper solids (about 70 mL). Separate the layers, then wash the organic layer with water (2×50 mL). Dry the organic portion over MgSO4. Filter, concentrate, and purify on silica gel (80 g) using 50-80% EtOAc/hexanes to afford 530 mg (63%) of the title compound as a white solid. MS (ES): 282 (M+1), 280 (M−1); 1H NMR (CDCl3): δ 8.44 (s, 1H), 7.76 (s, 1H), 7.40 (dd, 1H, J=8.4, 1.3 Hz), 7.37 (d, 1H, J=8.5 Hz), 5.64 (d, 1H, J=7.5 Hz), 4.42 (m, 1H), 3.11 (dd, 1H, J=15.2, 5.1 Hz), 2.98-2.80 (m, 2H), 2.59 (dd, 1H, J=15.4, 7.5 Hz), 2.38 (m, 1H), 2.17 (m, 1H), 2.02 (m, 1H), 1.21 (d, 6H, J=7.0 Hz); Chiral HPLC: Chiralcel OD-H 0.46×15 cm column, 15:85 EtOH/Heptane, 1.0 mL/min, 225 nm detection; Rt=7.37 min; >99% ee.

Workup

  1. customSparge the resulting solution with nitrogen for 15 min
  2. temperaturecool to room temperature
  3. customSeparate the layers
  4. washwash the organic layer with water (2×50 mL)
  5. dry with materialDry the organic portion over MgSO4
  6. filtrationFilter
  7. concentrationconcentrate
  8. custompurify on silica gel (80 g)

Sources & evidence

ORD record
ord-b05e64ab18e4491191f7b6e51f3e07ba
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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