Sodium hydride → HCID 68349180, compound

HRID 1850047Notes

Reaction equation

HRID 1850047 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]([NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:13])(OCC)=O)C.[NH:29]1[CH:33]=[C:32]([CH:34]=O)[CH:31]=[N:30]1>C1COCC1.CCOC(C)=O>[NH:29]1[CH:33]=[C:32](/[CH:34]=[CH:11]/[C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:13])[CH:31]=[N:30]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 51306731H-pyrazole-4-carbaldehydeHCID 86702812HCID 86702812, compound

Product 1

HCID 68349180HCID 68349180, compoundYield 72.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A 60% suspension of NaH in paraffin oil (192 mg, 5 mmol) was added portionwise to a solution of tert-butyl (2-(2-(diethoxyphosphoryl)acetamido)phenyl)carbamate (1.93 g, 5 mmol) in anhydrous THF (25 mL) at 0° C. The reaction mixture was stirred for 30 min before being warmed up to room temperature. 1H-pyrazole-4-carbaldehyde (400 mg, 4.16 mmol) dissolved in anhydrous THF (5 mL) was then added and the reaction mixture was stirred for 72 h under a nitrogen atmosphere. After completion of the reaction as indicated by HPLC, the mixture was diluted with EtOAc (80 mL) and quenched with a saturated NH4Cl solution (10 mL). The organic layer was separated and washed with water (40 mL) and brine (20 mL). It was dried over anhydrous Na2SO4 and the solid was filtered. The filtrate was evaporated under vacuum. The isolated crude was purified by silica gel column chromatography using a gradient of 0-100% EtOAc in hexanes to provide 986 mg of (E)-tert-butyl (2-(3-(1H-pyrazol-4-yl)acrylamido)phenyl)carbamate as a white solid. 1HNMR (300 MHz, CD3OD): δ 7.93 (broad s, 2H), 7.64 (d, 1H, J=15.6 Hz), 7.56 (d, 1H, J=7.2 Hz), 7.45 d, 1H, J=7.8 Hz), 7.11-7.24 (m, 2H), 6.59 (d, 1H, J=15.6 Hz), 1.50 (s, 9H), MS: ES+(M+Na)+: 351

Workup

  1. additionwas then added
  2. stirringthe reaction mixture was stirred for 72 h under a nitrogen atmosphere
  3. customAfter completion of the reaction
  4. customquenched with a saturated NH4Cl solution (10 mL)
  5. customThe organic layer was separated
  6. washwashed with water (40 mL) and brine (20 mL)
  7. dry with materialIt was dried over anhydrous Na2SO4
  8. filtrationthe solid was filtered
  9. customThe filtrate was evaporated under vacuum
  10. customThe isolated crude
  11. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-acffefd50dfc47008b3baac1b8e12054
Source dataset
uspto-grants-2015_02
Patent number
US08957066B2

Reaction notes

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