Water → HCID 66876063, compound

HRID 1666496Notes

Reaction equation

HRID 1666496 reaction equation
C(OP([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][C:17]2[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][N:18]=2)[CH:11]=1)(=O)OCC)C.[H-].[Na+].[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][C:36](=O)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].O>C1COCC1.O1CCOCCOCCOCCOCC1>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][C:36](=[CH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][C:17]3[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][N:18]=3)[CH:11]=2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 86623919HCID 86623919, compound

Product 1

HCID 66876063HCID 66876063, compoundYield 35.1%

Reagents, catalysts & solvents 2

HCID 3633615-Crown-5CatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

[3-(4-Methyl-pyridin-2-yloxy)-benzyl]-phosphonic acid diethyl ester (2.9 g, 8.6 mmol) from Step 3 and 1,4,7,10,13-pentaoxacyclopentadecane (15-Crown-5, 0.03 mL, 0.17 mmol) were combined in THF (10 mL). Sodium hydride (381 mg, 60% dispersion in mineral oil, 9.51 mmol) was added. The reaction was stirred for 30 minutes and then a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (1.90 g, 9.51 mmol) in THF (10 mL) was added. After 16 hours, water was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×200 mL) and the combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (10-30%, EtOAc:heptane) to afford the desired product (1.15 g, 35% yield) as a thick oil.

Workup

  1. waitAfter 16 hours
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×200 mL)
  4. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (10-30%, EtOAc:heptane)

Sources & evidence

ORD record
ord-f1476becc1fd4d03af4838ae43816e4a
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

Loading…