HCID 178419670, compound → HCID 178453608, compound

HRID 271362Notes

Reaction equation

HRID 271362 reaction equation
CON(C)[C:4]([C@@H:6]1[CH2:11][CH2:10][C@H:9]([CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:8][CH2:7]1)=[O:5].[CH2:22]([Mg]Br)[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>O1CCCC1>[C:24]1([CH2:23][CH2:22][C:4]([C@@H:6]2[CH2:7][CH2:8][C@H:9]([CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])[CH2:10][CH2:11]2)=[O:5])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

4

Reactant 2

HCID 178419670HCID 178419670, compoundHCID 178502720HCID 178502720, compound

Product 1

HCID 178453608HCID 178453608, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl [(cis-4-{[methoxy(methyl)amino]carbonyl}cyclohexyl)methyl]carbamate (4.51 g, 15.0 mmol) in dry tetrahydrofuran (15 ml) under nitrogen cooled in an ice-bath was added dropwise via syringe over five minutes a 1M solution of phenethyl magnesium bromide in tetrahydrofuran (60 ml, 60 mmol, 4 equivalents). The mixture was stirred 18 hours while warming from ice-bath temperature to ambient temperature. The reaction was quenched by addition of saturated ammonium chloride solution (60 ml). The mixture was diluted with ethyl acetate (240 ml) and the layers were separated. The organic layer was washed with water (60 ml), and brine (60 ml), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure to give crude product (6.30 g) as a yellow oil. The crude product was purified by flash column chromatography on silica gel, eluting with ethyl acetate/hexane (16:84 increasing to 25:75) to give tert-butyl {[cis-4-(3-phenylpropanoyl)cyclohexyl]methyl}carbamate (3.50 g, 68%) as a white solid: 1H NMR (CDCl3) 7.27 (2H, m), 7.18 (3H, m), 4.55 (1H, br s), 2.99 (2H, t, J 6.5 Hz), 2.88 (2H, t, J 7.5 Hz), 2.75 (2H, t, J 7.5 Hz), 2.44 (1H, m), 1.88 (2H, m), 1.53 (4H, m), 1.43 (9H, s), 1.26 (3H, t, J 7 Hz): MS: 346.3 (M+1).

Workup

  1. customThe reaction was quenched by addition of saturated ammonium chloride solution (60 ml)
  2. additionThe mixture was diluted with ethyl acetate (240 ml)
  3. customthe layers were separated
  4. washThe organic layer was washed with water (60 ml), and brine (60 ml)
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. customthe solvent evaporated under reduced pressure
  8. customto give crude product (6.30 g) as a yellow oil
  9. customThe crude product was purified by flash column chromatography on silica gel
  10. washeluting with ethyl acetate/hexane (16:84 increasing to 25:75)

Sources & evidence

ORD record
ord-55f89f8ed9be4321ad554f5a3067583d
Source dataset
uspto-grants-2008_11
Patent number
US07452893B2

Reaction notes

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