Iodine → HCID 86701271, compound

HRID 2276072Notes

Reaction equation

HRID 2276072 reaction equation
II.[C:3]([O:8][C@@H:9]1[C@@H:17]([CH2:18][CH2:19]I)[C:16](=[O:21])[O:15][CH2:14][C@H:13]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:12](=[O:30])[O:11][C@H:10]1[CH3:31])(=[O:7])[CH:4]([CH3:6])[CH3:5].F[C:33]1[CH:38]=[CH:37][C:36](I)=[CH:35][CH:34]=1>CN(C=O)C.CCOC(C)=O.[Zn].CC1C=CC=CC=1[P](C1C=CC=CC=1C)([Pd](Cl)(Cl)[P](C1=C(C)C=CC=C1)(C1C=CC=CC=1C)C1C=CC=CC=1C)C1C=CC=CC=1C>[C:3]([O:8][C@@H:9]1[C@@H:17]([CH2:18][CH2:19][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:16](=[O:21])[O:15][CH2:14][C@H:13]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:12](=[O:30])[O:11][C@H:10]1[CH3:31])(=[O:7])[CH:4]([CH3:6])[CH3:5]

Participants

8

Reactant 3

HCID 807IodineHCID 96054-FluoroiodobenzeneHCID 86701268HCID 86701268, compound

Product 1

HCID 86701271HCID 86701271, compoundYield 51%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 178424406HCID 178424406, compoundCatalystHCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To an oven-dried flask containing a magnetic stir bar was added freshly ground zinc dust (149 mg, 2.28 mmol) and a small volume of DMF (100 μL) was added to just cover the dust. Iodine (57 mg, 0.23 mmol) was added and the mixture stirred for 2 min and then warmed to 40° C. A solution of (3S,6S,7R,8R)-3-(tert-butoxycarbonylamino)-8-(2-iodoethyl)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (200 mg, 0.38 mmol) in DMF (1 mL) was added slowly at 40° C. After 15 min, the reaction mixture was cooled to ambient temperature (about 22° C.), and a solution of Pd((o-tol)3P)2Cl2 (7.5 mg, 0.01 mmol) and 1-fluoro-4-iodobenzene (58 uL, 0.49 mmol) in DMF (900 μL) was added to the reaction and the reaction was warmed back to 40° C. and stirring continued for 2.5 h. The mixture was cooled, diluted with EtOAc (2 mL) and filtered through a 0.45 μm fritted filter disc. The filtrate was diluted with EtOAc (20 mL), washed with saturated NaHCO3 solution (15 mL), dried over Na2SO4, filtered, and concentrated. Purification by column chromatography (SiO2, hexanes/EtOAc gradient) gave the title compound (92 mg, 51%) as a white glassy solid: 1H NMR (300 MHz, CDCl3) δ 7.31-7.14 (m, 3H), 7.14-7.04 (m, 2H), 5.46-5.15 (m, 2H), 5.06 (t, J=9.9 Hz, 1H), 4.91-4.72 (m, 2H), 3.61 (s, 1H), 2.76-2.48 (m, 3H), 2.40 (dt, J=13.8, 8.2 Hz, 1H), 2.17-1.99 (m, 1H), 1.73-1.52 (m, 1H), 1.45 (s, 9H), 1.25 (d, J=6.3 Hz, 3H), 1.16 (d, J=7.0 Hz, 6H); ESIMS m/z 500 ([M+Na]+).

Workup

  1. additionTo an oven-dried flask containing a magnetic stir bar
  2. waitAfter 15 min
  3. temperaturethe reaction mixture was cooled to ambient temperature (about 22° C.)
  4. temperaturethe reaction was warmed back to 40° C.
  5. stirringstirring
  6. waitcontinued for 2.5 h
  7. temperatureThe mixture was cooled
  8. filtrationfiltered through a 0.45 μm fritted filter disc
  9. additionThe filtrate was diluted with EtOAc (20 mL)
  10. washwashed with saturated NaHCO3 solution (15 mL)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customPurification by column chromatography (SiO2, hexanes/EtOAc gradient)

Sources & evidence

ORD record
ord-9ba797fd84b74535b1f91f14c3c7217a
Source dataset
uspto-grants-2015_09
Patent number
US09131690B2

Reaction notes

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