Dimethyl methylphosphonate → HCID 10929131, compound

HRID 742811Notes

Reaction equation

HRID 742811 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].C([Li])CCC.[C:13]([NH:32][C@@H:33]([C:39]([O:41][CH3:42])=[O:40])[CH2:34][C:35](OC)=[O:36])([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>O1CCCC1>[C:13]([NH:32][C@@H:33]([C:39]([O:41][CH3:42])=[O:40])[CH2:34][C:35](=[O:36])[CH2:1][P:2]([O:5][CH3:6])([O:3][CH3:4])=[O:7])([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 12958Dimethyl methylphosphonateHCID 10862336HCID 10862336, compoundHCID 178418339Butyllithium

Product 1

HCID 10929131HCID 10929131, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Dissolve dimethyl methylphosphonate (83mL, 0.766 mol) in anhydrous tetrahydrofuran (800 mL), cool to -78° C. and place under an inert atmosphere. Add, by dropwise addition over 15 minutes, n-butyllithium (306 mL of a 2.5M solution, 0,766 mol). Stir the resulting clear solution for a further 0.5 hour. While maintaining the solution at -78° C, add by dropwise addition over 15 minutes, to another solution of (R)-dimethyl N-tritylaspartate (71 g, 0.182 mol) in anhydrous tetrahydrofuran (200 mL) also at -78° C. Stir for a further 0.5 hours, quench with acetic acid (45 mL) and warm to room temperature. Add ethyl acetate (500 mL) and saturated sodium bicarbonate (250 mL). Separate the organic phase, filter through silica gel and evaporate the solvent to give a solid residue. Crystallize (t-butylmethyl ether/hexane) to give the title compound as a white solid (61.0 g, 69%). 1H NMR (CDCl3) δ7.5-7.25 (m, 15 H), 3.82 (s, 3H), 3.79 (s, 3H), 3.75 (t, 3H), 3.08 (d, 2H), 2.88 (m, 2H), 1.65 (bs, 1H).

Workup

  1. additionAdd, by dropwise addition over 15 minutes
  2. temperatureWhile maintaining the solution at -78° C
  3. stirringStir for a further 0.5 hours
  4. customquench with acetic acid (45 mL)
  5. temperaturewarm to room temperature
  6. customSeparate the organic phase
  7. filtrationfilter through silica gel
  8. customevaporate the solvent
  9. customto give a solid residue
  10. customCrystallize (t-butylmethyl ether/hexane)

Sources & evidence

ORD record
ord-2944033efe284ae6afa7eaa4a4ad7834
Source dataset
uspto-grants-1996_09
Patent number
US05554773

Reaction notes

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