Tetramethyltin → HCID 70159519, compound

HRID 844215Notes

Reaction equation

HRID 844215 reaction equation
[C:1]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([O:24][C:25]([NH:27][C@@H:28]([CH3:41])[CH2:29][N:30]1[C:38]2[C:33](=[CH:34][C:35]([F:40])=[C:36](I)[CH:37]=2)[CH2:32][CH2:31]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C[Sn](C)(C)C.[F-].[K+]>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:20]([O:24][C:25]([NH:27][C@@H:28]([CH3:41])[CH2:29][N:30]1[C:38]2[C:33](=[CH:34][C:35]([F:40])=[C:36]([CH3:1])[CH:37]=2)[CH2:32][CH2:31]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]

Participants

7

Reactant 4

HCID 11661TetramethyltinHCID 11776TriphenylphosphineHCID 522689Potassium FluorideHCID 70158693HCID 70158693, compound

Product 1

HCID 70159519HCID 70159519, compoundYield 275.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Triphenylphosphine (66 mg, 0.2 mmol) was added in one portion to a stirred solution of palladium(II) acetate (18 mg, 0.06 mmol) in tetrahydrofuran (2.5 mL) under Ar. The mixture was stirred for 5 min then a solution of (S)-1-[2-(tert-butoxycarbonylamino)propyl)-5-fluoro-6-iodoindoline (0.45 g, 1.1 mmol) in tetrahydrofuran (7.5 mL) was added in one portion. The mixture was stirred for 10 min then tetramethyltin (2.0 g, 11 mmol) was added in one portion. The mixture was heated to reflux and stirred for 168 h. After cooling to room temperature, the mixture was poured into an aqueous solution of potassium fluoride (50 mL) and extracted with ethyl acetate (2×30 mL). The combined organic extracts were dried (magnesium sulfate), filtered and concentrated in vacuo to leave a crude oil. The oil was purified by column chromatography [SiO2; ethyl acetate-heptane (1:19)] to give the product (0.17 g, 50%) as a yellow solid; NMR δH (400 MHz, CDCl3) 6.74 (1H, d, J 9 Hz), 6.22 (1H, d, J 5.9 Hz), 4.57 (1H, br. s), 3.82-3.91 (1H, m), 3.31-3.40 (2H, m), 2.89-2.99 (4H, m), 2.05 (3H, s), 1.44 (9H, s), 1.22 (3H, d, J 6.5 Hz).

Workup

  1. stirringThe mixture was stirred for 10 min
  2. temperatureThe mixture was heated
  3. temperatureto reflux
  4. stirringstirred for 168 h
  5. extractionextracted with ethyl acetate (2×30 mL)
  6. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto leave a crude oil
  10. customThe oil was purified by column chromatography [SiO2; ethyl acetate-heptane (1:19)]

Sources & evidence

ORD record
ord-74e875dd3c07424dab7cc13485273d50
Source dataset
uspto-grants-2002_04
Patent number
US06380238B1

Reaction notes

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