Sodium hydride → 3-[1-(Tert-butoxycarbonyl)piperidin-4-ylidene]propanoic acid

HRID 1386749Notes

Reaction equation

HRID 1386749 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl-].[C:16]([CH2:19][CH2:20]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:18])=[O:17].[H-].[Na+]>CS(C)=O.C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[CH:20][CH2:19][C:16]([OH:18])=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 21180642(3-Carboxypropyl)(triphenyl)phosphanium chloride

Product 1

HCID 211806823-[1-(Tert-butoxycarbonyl)piperidin-4-ylidene]propanoic acidYield 25%

Reagents, catalysts & solvents 1

HCID 21830753dimethylsulfoxide THFSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 7.53 g (37.8 mmol) of 1-t-butoxycarbonyl-piperidin-4 one and 14 g (37.8 mmol) of (3-carboxypropyl)triphenyl-phosphonium chloride (from EXAMPLE 98, Step A) were dissolved in 100 mL of 1:1 v/v DMSO/THF. The mixture was cooled to 0° C. and was then added to 2 g (83.2 mmol) of dry 95% sodium hydride powder at 0° C. over a 10 min period. After stirring this mixture at 0 ° C. for 20 h, the reaction was quenched with H2O, treated with sat'd NaCl and extracted 2× with CH2Cl2. The aqueous phase was acidified to pH 1 with 1 N HCl, and extracted 3× with CH2Cl2. The combined organic layers were washed with sat'd NaCl and H2O, dried over Na2SO4, filtered and the filtrate concentrated. The residue was purified by column chomatography on 150 g of silica using a gradient of 25-50% acetone/hexanes (v/v), to give 2.4 g (25%) of the title compound: 1H NMR (500 _MHz) δ 1.47 (s, 9H1.2.21 (d, J=5.5,44H), 3.12 (d, J=7.3,22H), 3.42 (d, J=5.7, 4H), 5.41 (t, J=7.1, 11H).

Workup

  1. customthe reaction was quenched with H2O
  2. additiontreated with sat'd NaCl
  3. extractionextracted 2× with CH2Cl2
  4. extractionextracted 3× with CH2Cl2
  5. washThe combined organic layers were washed with sat'd NaCl and H2O
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated
  9. customThe residue was purified by column chomatography on 150 g of silica using a gradient of 25-50% acetone/hexanes (v/v)

Sources & evidence

ORD record
ord-7c54bee548694653a7935cc012a017b6
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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