HCID 67251019, compound → HCID 67248548, compound

HRID 515712Notes

Reaction equation

HRID 515712 reaction equation
[CH:1]1([C:6]2[CH:31]=[CH:30][C:9]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][C:18]4[N:17]5[CH2:21][CH2:22][CH:23]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[C:16]5=[C:15](I)[C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:32]([F:35])([F:34])[F:33])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl-].[CH3:37][Zn+]>C1COCC1>[CH:1]1([C:6]2[CH:31]=[CH:30][C:9]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][C:18]4[N:17]5[CH2:21][CH2:22][CH:23]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[C:16]5=[C:15]([CH3:37])[C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:32]([F:35])([F:34])[F:33])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 67251019HCID 67251019, compoundHCID 178477797HCID 178477797, compound

Product 1

HCID 67248548HCID 67248548, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

Methyl 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-iodo-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (0.923 g, 1.54 mmol) was mostly dissolved in anhydrous THF (15.4 mL) to give a turbid suspension which was degassed with N2 for about 15 min. Bis(tri-t-butylphosphine)Pd(0) (0.071 g, 0.139 mmol) and 2.0 M methylzinc chloride in THF (2.318 mL, 4.64 mmol) were added at 25° C. The reaction mixture was sealed and heated at 70° C. to give a dark suspension. After 2 h at 70° C., the reaction mixture was cooled to 25° C., quenched with NaHCO3 (4 mL), stirred for 5 min, and filtered through a celite pad. The filtrate was diluted with MTBE, washed with H2O (twice), brine, and dried over MgSO4. The solvent was evaporated in vacuo to give a solid. The solid was dissolved in DCM/hexanes (1:1) and purified by silica gel column chromatography to give the titled compound (0.582 g) as a white solid. LCMS m/z=486.5 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 1.58-1.66 (m, 2H), 1.67-1.79 (m, 2H), 1.80-1.91 (m, 2H), 2.05-2.14 (m, 2H), 2.23 (s, 3H), 2.26-2.36 (m, 1H), 2.51 (dd, J=−15.92, 10.11 Hz, 1H), 2.82-2.90 (m, 1H), 2.94 (dd, J=15.79, 4.67 Hz, 1H), 3.32-3.43 (m, 1H), 3.73 (s, 3H), 3.75-3.80 (m, 1H), 3.92-4.01 (m, 1H), 4.02-4.10 (m, 1H), 5.09 (s, 2H), 6.86 (dd, J=8.72, 2.40 Hz, 1H), 7.04 (d, J=2.27 Hz, 1H), 7.10 (d, J=8.84 Hz, 1H), 7.47 (d, J=8.08 Hz, 1H), 7.61 (d, J=8.08 Hz, 1H), 7.71 (s, 1H).

Workup

  1. customto give a turbid suspension which
  2. customwas degassed with N2 for about 15 min
  3. customThe reaction mixture was sealed
  4. customto give a dark suspension
  5. temperaturethe reaction mixture was cooled to 25° C.
  6. customquenched with NaHCO3 (4 mL)
  7. filtrationfiltered through a celite pad
  8. additionThe filtrate was diluted with MTBE
  9. washwashed with H2O (twice), brine
  10. dry with materialdried over MgSO4
  11. customThe solvent was evaporated in vacuo
  12. customto give a solid
  13. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-5529ddc07d5f4715a40744b6997d21fd
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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