Methyl iodide → HCID 59514587, compound

HRID 1363862Notes

Reaction equation

HRID 1363862 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]=[O:15])[C@H:10]([CH2:16][OH:17])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:21]>CN(C=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]=[O:15])[C@H:10]([CH2:16][O:17][CH3:21])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59514579HCID 59514579, compound

Product 1

HCID 59514587HCID 59514587, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 0° C. solution of alcohol 22 (0.502 g, 2.14 mmol) in dry DMF (20 mL) was added NaH (95%, 0.154 g, 6.43 mmol) in one portion. After stirring 5 min, iodomethane (0.319 g, 2.25 mmol) was added (drop-wise) and the mixture stirred for 20 min at 0° C. then at ambient temperature for 1.5 h. The excess NaH was destroyed by the careful addition of water and the solution was diluted with 40 mL each of water and saturated NaHCO3. The aqueous mixture was extracted with ether (2×40 mL) and ethyl acetate (2×40 mL). The combined extracts were washed with brine (50 mL), dried (K2CO3) and concentrated to give a brown oil that was purified by column chromatography (silica gel, MeOH:CHCl3, gradient 1:199 to 1:49) to afford 23 as a pale colored oil (0.360 g, 69% yield). 1H NMR (400 MHz, CDCl3): δ 2.00-2.12 (m, 1.3H), 2.18 (dd, J=3.7, 11.7 Hz, 0.7H), 2.80-2.92 (m, 2H), 2.93-3.02 (m, 1H), 3.29-3.38 (m, 3H), 3.41-3.76 (m, 5H), 4.16 (bd, 0.7H), 4.60 (m, 0.3H), 7.25-7.35 (m, 5H), 8.04 (s, 0.7H), 8.07 (s, 0.3H); 13C NMR (100 MHz, CDCl3): δ 36.7, 42.7, 47.0, 52.3, 53.2, 53.7, 54.1, 58.8, 59.0, 62.5, 62.6, 69.5, 70.6, 127.2, 128.3, 128.7, 137.7, 161.3, 161.9. HRMS Calcd. for [C14H20N2O2+H+] 249.1603. Found 249.1598. [α]D25-37.6 (c 0.036, CHCl3).

Workup

  1. stirringthe mixture stirred for 20 min at 0° C.
  2. waitat ambient temperature for 1.5 h
  3. customThe excess NaH was destroyed by the careful addition of water
  4. additionthe solution was diluted with 40 mL each of water and saturated NaHCO3
  5. extractionThe aqueous mixture was extracted with ether (2×40 mL) and ethyl acetate (2×40 mL)
  6. washThe combined extracts were washed with brine (50 mL)
  7. dry with materialdried (K2CO3)
  8. concentrationconcentrated
  9. customto give a brown oil that
  10. customwas purified by column chromatography (silica gel, MeOH:CHCl3, gradient 1:199 to 1:49)

Sources & evidence

ORD record
ord-176b32289ad345e4aec3e64bb77d4996
Source dataset
uspto-grants-2011_02
Patent number
US07887784B2

Reaction notes

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