Trimethyl phosphonoacetate → HCID 69858985, compound

HRID 1860294Notes

Reaction equation

HRID 1860294 reaction equation
[CH3:1][O:2][C:3]([CH2:5]P(OC)(OC)=O)=[O:4].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH:22]([C:24]1[CH:29]=[CH:28][C:27](/[C:30](/[C:40]2[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=2)=[C:31](\[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)/[CH2:32][CH3:33])=[CH:26][CH:25]=1)=O>C1COCC1.[Cl-].[Na+].O>[F:46][C:43]1[CH:42]=[CH:41][C:40]([C:30]([C:27]2[CH:26]=[CH:25][C:24]([CH:22]=[CH:5][C:3]([O:2][CH3:1])=[O:4])=[CH:29][CH:28]=2)=[C:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:32][CH3:33])=[CH:45][CH:44]=1

Participants

6

Reactant 3

HCID 80029Trimethyl phosphonoacetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 12085902HCID 12085902, compound

Product 1

HCID 69858985HCID 69858985, compoundYield 90.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of trimethyl phosphonoacetate (412 mg, 2.26 mmol) in THF (15 mL) at 0° C. was added 1M sodium bis(trimethylsilyl)amide in THF (2.26 mL, 2.26 mmol) dropwise. After stirring 15 min the mixture was cooled to −78° C. and a solution of aldehyde (4) (625 mg, 1.89 mmol) in THF (8 mL) was added dropwise. The solution was allowed to warm to rt. After stirring 4 h, brine was added and the mixture was extracted with EtOAc. The combined organic layers were washed with water, brine, and dried (MgSO4). The solvent was removed under reduced pressure and the residue was chromatographed (silica gel, 7.5 to 15% EtOAc/hexanes) to give the ester (5) as a white solid (658 mg, 90%): 1 H NMR (CDCl3) δ 7.52 (d, J=16.1 Hz, 1 H), 7.15 (m, 11 H), 6.86 (d, J=8.1 Hz, 2 H), 6.28 (d, J=16.1 Hz, 1 H), 3.76 (s, 3 H), 2.47 (q, J=7.7 Hz, 2 H), 0.93 (t, J=7.7 Hz, 3 H); APcI m/z: 428 (M+H+CH3CN+, 100%).

Workup

  1. temperatureto warm to rt
  2. stirringAfter stirring 4 h
  3. extractionthe mixture was extracted with EtOAc
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried (MgSO4)
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was chromatographed (silica gel, 7.5 to 15% EtOAc/hexanes)

Sources & evidence

ORD record
ord-9886edc9a2ef4d41a662626952c86ab6
Source dataset
uspto-grants-2003_03
Patent number
US06528681B2

Reaction notes

Loading…