Toluene → HCID 86709919, compound

HRID 2179125Notes

Reaction equation

HRID 2179125 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:17]=[CH:16][C:8]([CH2:9][NH:10][C:11]([CH:13]2[CH2:15][CH2:14]2)=[O:12])=[CH:7][CH:6]=1.[CH2:18](Br)[C:19]#[CH:20].C1(C)C=CC=CC=1>CCOCC.C1COCC1>[CH3:3][O:4][C:5]1[CH:17]=[CH:16][C:8]([CH2:9][N:10]([CH2:20][C:19]#[CH:18])[C:11]([CH:13]2[CH2:14][CH2:15]2)=[O:12])=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 7842Propargyl bromideHCID 24758Sodium hydride2×HCID 897392HCID 897392, compound

Product 1

HCID 86709919HCID 86709919, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

Sodium hydride (60% in mineral oil, 709 mg, 17.72 mmol) was washed with dry ether (2×20 mL) and then suspended in dry THF (30 mL) and cooled with ice-water. Crude N-(4-methoxybenzyl)cyclopropanecarboxamide from last step in THF (5 mL) was added dropwise at 5° C. to the sodium hydride suspension. The reaction mixture was stirred at 5° C. for 20 min. A solution of propargyl bromide in toluene (80% wt., 2.69 mL, 24.17 mmol) was added dropwise with a syringe. The ice bath was removed and the mixture was stirred at room temperature overnight. The mixture was poured into ice-water (100 mL) and extracted with DCM (3×100 mL). The organic phases were combined and washed with brine (2×50mL), dried with anhydrous MgSO4, filtered and evaporated to dryness, then purified by silica gel column chromatography, eluting with MeOH/DCM (0-2%) to give the product (2.43 g, 62.0% yield), LRMS ESI (M+H+) 244.

Workup

  1. customThe ice bath was removed
  2. stirringthe mixture was stirred at room temperature overnight
  3. additionThe mixture was poured into ice-water (100 mL)
  4. extractionextracted with DCM (3×100 mL)
  5. washwashed with brine (2×50mL)
  6. dry with materialdried with anhydrous MgSO4
  7. filtrationfiltered
  8. customevaporated to dryness
  9. custompurified by silica gel column chromatography
  10. washeluting with MeOH/DCM (0-2%)

Sources & evidence

ORD record
ord-431151b66bea424b9f1eadd8676a0862
Source dataset
uspto-grants-2015_06
Patent number
US09067963B2

Reaction notes

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