Sodium hydride → HCID 178512009, compound

HRID 659127Notes

Reaction equation

HRID 659127 reaction equation
C[O:2][C:3]([CH2:5]P(OC)(OC)=O)=[O:4].[H-].[Na+].[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][C:16]=1[C:27]([NH:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([CH:36]=O)[CH:31]=1)=[NH:28].C([O-])(O)=O.[Na+]>C1COCC1>[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[CH:17][C:16]=1[C:27]([NH:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:5][C:3]([OH:2])=[O:4])[CH:33]=[CH:34][CH:35]=1)=[NH:28]

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 80029Trimethyl phosphonoacetateHCID 516892Sodium BicarbonateHCID 178512012HCID 178512012, compound

Product 1

HCID 178512009HCID 178512009, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Trimethyl phosphonoacetate (176 mg, 0.97 mmol) in THF (1.5 mL) was added dropwise (caution—vigorous reaction!) to sodium hydride (60% in oil) (58 mg, 1.46 mmol) under an atmosphere of nitrogen at 0° C. The reaction mixture was stirred for 15 minutes at 0° C. and then aldehyde (57) (307 mg, 0.97 mmol) in THF (1.50 mL) was added. After 3-hours further sodium hydride (60% in oil) (1.5 eq) was added and the reaction mixture stirred at ambient temperature overnight. Saturated NaHCO3 solution was added and washed with EtOAc. The aqueous layer was acidified to pH 1 using 1.2 M HCl and extracted with EtOAc. The aqueous layer was then neutralised to pH 7 and extracted into EtOAc. The organic layers were combined, dried (MgSO4) and the solvent concentrated in vacuo. The residue was purified by Flash Master Jones Chromatography using a 2 g silica cartridge and a gradient of EtOAc in heptane and MeOH in EtOAc to yield the title compound. Yield: 25 mg, 7%; LC-MS tr 1.77 min; HPLC Purity: 91%; MS (ES+) m/z 361 (M+H); NMR (400 MHz; MeOH): δ 6.6 (d, 7.35-7.80 (m, 11H), 8.05 (m, 1H), 8.15 (d, 1H)

Workup

  1. stirringthe reaction mixture stirred at ambient temperature overnight
  2. washwashed with EtOAc
  3. extractionextracted with EtOAc
  4. extractionextracted into EtOAc
  5. dry with materialdried (MgSO4)
  6. concentrationthe solvent concentrated in vacuo
  7. customThe residue was purified by Flash Master Jones Chromatography

Sources & evidence

ORD record
ord-eff0ffa522ea433cbf0f3c4b61a2a6cf
Source dataset
uspto-grants-2011_12
Patent number
US08080567B2

Reaction notes

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