Sodium hydride → rac-ethyl (1R,2R)-2-(4-aminophenyl)cyclopropane-1-carboxylate

HRID 2174211Notes

Reaction equation

HRID 2174211 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[NH2:9][C:10]1[CH:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][CH:11]=1>CS(C)=O>[NH2:9][C:10]1[CH:11]=[CH:12][C:13]([C@@H:16]2[CH2:4][C@H:17]2[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 736317Ethyl 4-aminocinnamate

Product 1

HCID 68767952rac-ethyl (1R,2R)-2-(4-aminophenyl)cyclopropane-1-carboxylate

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a suspension of sodium hydride (36 mg, 0.89 mmol) in DMSO (2 mL) was added the solid trimethyl sulfoxonium iodide (185 mg, 1.05 mmol). The mixture was stirred for 25 min before a solution of ethyl (E)-3-(4-aminophenyl)prop-2-enoate (100 mg, 0.52 mmol) in DMSO (2 mL) was added quickly at RT. The mixture was left to stir overnight. The bulk mixture was quenched with NH4Cl (sat.) and the mixture diluted with water and EtOAc. The layers were separated and the aqueous layer extracted into EtOAc (3×30 mL). The organic fractions were combined, dried with brine then MgSO4 and the solvent removed. Flash chromatography on silica gel, eluting with 20-50% ethyl acetate gradient in n-heptane, gave ethyl (1R,2R)-2-(4-aminophenyl)cyclopropanecarboxylate, 70 mg. 1H NMR (400 MHz, CDCl3) δ 6.96-6.89 (m, 2H), 6.68-6.61 (m, 2H), 4.17 (q, J=7.1 Hz, 2H), 2.44 (ddd, J=9.2, 6.6, 4.2 Hz, 1H), 1.80 (ddd, J=8.4, 5.2, 4.2 Hz, 1H), 1.53 (ddd, J=9.2, 5.2, 4.5 Hz, 1H), 1.28 (t, J=7.1 Hz, 3H), 1.24 (ddd, J=8.3, 6.6, 4.5 Hz, 1H).

Workup

  1. additionwas added quickly at RT
  2. waitThe mixture was left
  3. customThe bulk mixture was quenched with NH4Cl (sat.)
  4. additionthe mixture diluted with water and EtOAc
  5. customThe layers were separated
  6. extractionthe aqueous layer extracted into EtOAc (3×30 mL)
  7. dry with materialdried with brine
  8. customMgSO4 and the solvent removed
  9. washFlash chromatography on silica gel, eluting with 20-50% ethyl acetate gradient in n-heptane

Sources & evidence

ORD record
ord-e5828ed443d141db9fd38cdc33533811
Source dataset
uspto-grants-2015_06
Patent number
US09060515B2

Reaction notes

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