Sodium hydride → HCID 69841045, compound

HRID 1479014Notes

Reaction equation

HRID 1479014 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.[C:37]([N:44]1[CH2:49][CH2:48][C:47](=O)[CH2:46][CH2:45]1)([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38]>C1COCC1.O>[C:40]([O:39][C:37]([N:44]1[CH2:49][CH2:48][C:47](=[CH:12][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[C:5]([O:4][CH3:3])=[O:21])[CH2:46][CH2:45]1)=[O:38])([CH3:43])([CH3:41])[CH3:42]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 54498727HCID 54498727, compound

Product 1

HCID 69841045HCID 69841045, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (526 mg; 12.05 mmol; 1.2 eq.) was added to a cold (0° C.) solution of 2-(diethoxy-phosphorylmethyl)-benzoic acid methyl ester (3.45 g; 12.05 mmol; 1.2 eq.) and 15-crown-5 (60 μL; 0.30 mmol; 0.03 eq.) in THF (10 mL) and the reaction mixture was stirred at room temperature for 30 min whereupon a solution of 1-boc-piperidin-4-one (2 g; 10.04 mmol; 1 eq.) in THF (10 mL) was added dropwise over 10 min at 0° C. The reaction mixture was stirred at room temperature for 2 days then diluted with water and extracted with EA (2×). The combined organic phase was washed with 1M (NaOH) then brine, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (heptanes/EA, 95/5 to 50/50) afforded the title compound (450 mg, 14%) as a white solid. UPLC/MS: (MS+) 332.3 ([M+H]+).

Workup

  1. additionwas added dropwise over 10 min at 0° C
  2. extractionextracted with EA (2×)
  3. washThe combined organic phase was washed with 1M (NaOH)
  4. dry with materialbrine, dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification by column chromatography (heptanes/EA, 95/5 to 50/50)

Sources & evidence

ORD record
ord-647ab0e395594591bb960d5ca0057c2a
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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