Acetaldehyde → Ethyl 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-but-2-enoic acid ethyl ester

HRID 1789872Notes

Reaction equation

HRID 1789872 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:31])[CH:7](P(OCC)(OCC)=O)[CH2:8][C:9]1[CH:10]=[N:11][C:12]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:13][CH:14]=1)[CH3:4].C(=O)C.[CH2:35]1[CH2:39]O[CH2:37][CH2:36]1>>[CH2:3]([O:5][C:6](=[O:31])[C:7]([CH2:8][C:9]1[CH:10]=[N:11][C:12]([NH:15][C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])=[CH:13][CH:14]=1)=[C:35]([CH2:36][CH3:37])[CH3:39])[CH3:4]

Participants

5

Reactant 4

HCID 177Acetaldehyde2×HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 220360143-(6-Tert-butoxycarbonylamino-pyridin-3-yl)-2-(diethoxyphosphoryl)-propionic acid ethyl ester

Product 1

HCID 57028003Ethyl 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-but-2-enoic acid ethyl ester

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (278.8 mg, 60% in mineral oil, 6.97 mmol) in THF (25 mL) at 0° C. was added a solution of 3-(6-tert-butoxycarbonylamino-pyridin-3-yl)-2-(diethoxyphosphoryl)-propionic acid ethyl ester (2.5 g, 5.81 mmol) in THF (30 mL). The reaction mixture was allowed to stir at 0° C. for 1 h. To the reaction was added acetaldehyde (512 mg, 11.6 mmol) dropwise at 0° C. The reaction mixture was allowed to warm to room temperature and then stir for 16 h. Acetaldehyde (2.0 g) was added to the reaction vessel and the reaction mixture was allowed to stir at room temperature for an additional 16 h. The reaction was quenched with the slow addition of saturated aqueous ammonium chloride (30 mL). The mixture was extracted with EtOAc, washed with brine and dried to afford the crude product. The crude product was purified by column chromatography (EtOAc/hexane, 1:8) to give ethyl 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-but-2-enoic acid ethyl ester as a mixture of isomers (1.1 g, 60%).

Workup

  1. temperatureto warm to room temperature
  2. stirringstir for 16 h
  3. stirringto stir at room temperature for an additional 16 h
  4. customThe reaction was quenched with the slow addition of saturated aqueous ammonium chloride (30 mL)
  5. extractionThe mixture was extracted with EtOAc
  6. washwashed with brine
  7. customdried
  8. customto afford the crude product
  9. customThe crude product was purified by column chromatography (EtOAc/hexane, 1:8)

Sources & evidence

ORD record
ord-fb4ce0cb2e1f4a64b1bdf58712ab1ba0
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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