Sodium hydride → HCID 89650329, compound

HRID 1479016Notes

Reaction equation

HRID 1479016 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:21])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12]P(OCC)(OCC)=O.C1OCCOCCOCCOCCOC1.[CH3:37][N:38]1[CH2:43][CH2:42][C:41](=O)[CH2:40][CH2:39]1>C1COCC1>[CH3:3][O:4][C:5](=[O:21])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH:12]=[C:41]1[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 740491-Methyl-4-piperidoneHCID 54498727HCID 54498727, compound

Product 1

HCID 89650329HCID 89650329, compoundYield 21.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

NaH (55-65%, 231 mg; 5.3 mmol; 1.2 eq.) was added to a cold (0° C.) solution of 2-(diethoxy-phosphorylmethyl)-benzoic acid methyl ester (from Intermediate B11 step 1) (1.52 g; 5.3 mmol; 1.2 eq.) and 15-crown-5 (26 μL; 0.13 mmol; 0.03 eq.) in THF (5 mL) and the reaction mixture was stirred at room temperature for 30 minutes whereupon a solution of 1-methyl-piperidin-4-one (500 mg; 4.42 mmol; 1 eq.) in THF (5 mL) was added dropwise over 10 minutes at 0° C. The resulting mixture was stirred at room temperature for 3.5 hours then concentrated in vacuo. The residue was taken up in water and extracted with EA (2×). The combined organics were washed with 1M NaOH then brine, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (DCM to 10% MeOH in DCM) afforded the title compound (230 mg, 21%) as a yellow oil. UPLC/MS: (MS+) 246.3 ([M+H]+).

Workup

  1. additionwas added dropwise over 10 minutes at 0° C
  2. concentrationthen concentrated in vacuo
  3. extractionextracted with EA (2×)
  4. washThe combined organics were washed with 1M NaOH
  5. dry with materialbrine, dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification by column chromatography (DCM to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-cbb673bff9f54a8cbc317b2c3581dc6e
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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