Methyl iodide → HCID 69058266, compound

HRID 2100586Notes

Reaction equation

HRID 2100586 reaction equation
[H-].[Na+].[OH:3][CH2:4][CH2:5][N:6]1[C@H:15]2[CH2:16][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][C@@H:14]2[C:13]2[CH:12]=[CH:11][CH:10]=[C:9]([C:26]([F:29])([F:28])[F:27])[C:8]=2[C:7]1=[O:30].I[CH3:32]>C1COCC1.COC(C)(C)C>[CH3:32][O:3][CH2:4][CH2:5][N:6]1[C@H:15]2[CH2:16][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][C@@H:14]2[C:13]2[CH:12]=[CH:11][CH:10]=[C:9]([C:26]([F:27])([F:29])[F:28])[C:8]=2[C:7]1=[O:30]

Participants

6

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 69054993HCID 69054993, compound

Product 1

HCID 69058266HCID 69058266, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 15413tert-Butyl methyl etherSolvent2×

Procedure

To a suspension of sodium hydride (8 mg of 60% dispersion in mineral oil, hexane-washed, 0.20 mmol) in 2 mL of THF was added (3aR,9bS)-tert-butyl 4-(2-hydroxyethyl)-5-oxo-6-(trifluoromethyl)-3,3a,4,5-tetrahydro-1H-pyrrolo[3,4-c]isoquinoline-2(9bH)-carboxylate from Example 20, Part A (40 mg, 0.10 mmol) in 2 mL THF. The reaction was stirred for 20 min, at which time gas evolution had ceased. Then there was added iodomethane (0.125 mL of a 2M solution in tert-butyl methyl ether, 0.25 mmol) and the reaction was allowed to stir at ambient temperature for 18 h. TLC analysis showed that starting material remained. Additional sodium hydride (8 mg of 60% dispersion in mineral oil, 0.20 mmol) and iodomethane (0.125 mL of a 2M solution in tert-butyl methyl ether, 0.25 mmol) were added and the reaction was allowed to stir at 40° C. for 2 h. The reaction was quenched with 10 mL of 1N HCl and extracted with EtOAc. The organics were washed with sat'd aq NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (230-400 mesh silica gel, elution with 4:1 hexane/EtOAc) to afford 15 mg (37%) of the title compound. 1H NMR (CDCl3): δ 7.79 (d, 1H, J=7.7 Hz), 7.57-7.52 (m, 2H), 7.25-7.22 (m, 1H), 4.15-4.10 (m, 1H), 4.08-3.98 (m, 2H), 3.82-3.77 (m, 1H), 3.61-3.54 (m, 2H), 3.50-3.27 (overlapping m, 4H), 3.31 and 3.28 (singlets, 3H), 1.50 (s, 9H).

Workup

  1. stirringto stir at ambient temperature for 18 h
  2. stirringto stir at 40° C. for 2 h
  3. customThe reaction was quenched with 10 mL of 1N HCl
  4. extractionextracted with EtOAc
  5. washThe organics were washed with sat'd aq NaHCO3 and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (230-400 mesh silica gel, elution with 4:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-61f35147fba54d718a91b507271994d2
Source dataset
uspto-grants-2009_08
Patent number
US07572805B2

Reaction notes

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