Methyl iodide → HCID 66669442, compound

HRID 244540Notes

Reaction equation

HRID 244540 reaction equation
[CH3:1][C:2]([Si:5]([CH3:19])([CH3:18])[O:6][CH2:7][C@@H:8]1[CH2:13][N:12]2[CH2:14][CH2:15][CH2:16][C@H:11]2[C:10](=[O:17])[NH:9]1)([CH3:4])[CH3:3].[H-].[Na+].I[CH3:23]>CN(C)C=O>[CH3:4][C:2]([Si:5]([CH3:19])([CH3:18])[O:6][CH2:7][C@@H:8]1[CH2:13][N:12]2[CH2:14][CH2:15][CH2:16][C@H:11]2[C:10](=[O:17])[N:9]1[CH3:23])([CH3:1])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66669456HCID 66669456, compound

Product 1

HCID 66669442HCID 66669442, compoundYield 97.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

(3S,8aS)-3-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)hexahydropyrrolo[1,2-a]pyrazin-1(2H)-one (1.51 g, 5.32 mmol) in dimethylformamide (8 mL) was added to an ice-cooled suspension of sodium hydride (60 wt. % dispersion in oil; 213 mg, 5.32 mmol) in dimethylformamide (8 mL). The mixture was stirred at 0° C. for 0.25 h and then iodomethane (0.332 mL, 5.32 mmol) was added dropwise. The mixture was stirred at room temperature for 0.5 h and then was stirred at 70° C. for 2 h. The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and water. The aqueous portion was extracted with ethyl acetate. The combined organic portion was dried over sodium sulfate, filtered and concentrated in vacuo to afford (3S,8aS)-3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-methylhexahydropyrrolo[1,2-a]pyrazin-1(2H)-one as a yellow oil (1.552 g, 5.21 mmol) which was dissolved in tetrahydrofuran (20 mL) and treated with tetrabutylammonium fluoride (1.0M solution in tetrahydrofuran; 10.4 mL, 10.4 mmol) for 2 h at room temperature. The mixture was concentrated in vacuo and purified by column chromatography (10% methanol in dichloromethane) to afford (3S,8aS)-3-(hydroxymethyl)-2-methylhexahydropyrrolo[1,2-a]pyrazin-1(2H)-one as a yellow oil (496 mg, 2.70 mmol, 51% yield from (3S,8aS)-3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)hexahydropyrrolo[1,2-α]pyrazin-1(2H)-one). 1H NMR (400 MHz, CDCl3): 3.98-3.93 (m, 1H), 3.86 (dd, 1H), 3.61-3.55 (m, 1H), 3.29-3.25 (m, 1H), 3.09-3.03 (m, 1H), 3.03-2.97 (m, 1H), 3.02 (s, 3H), 2.93 (dd, 1H), 2.87-2.79 (m, 1H), 2.32-2.21 (m, 1H), 2.00-1.86 (m, 2H), 1.83-1.64 (m, 1H); MS (EI) for C9H16N2O2: 185 (MH+).

Workup

  1. temperaturecooled
  2. stirringThe mixture was stirred at room temperature for 0.5 h
  3. stirringwas stirred at 70° C. for 2 h
  4. concentrationThe mixture was concentrated in vacuo
  5. customthe residue was partitioned between ethyl acetate and water
  6. extractionThe aqueous portion was extracted with ethyl acetate
  7. dry with materialThe combined organic portion was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-03d4dca25cef4ce6bac927e4b1a94f9c
Source dataset
uspto-grants-2014_02
Patent number
US08658654B2

Reaction notes

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