(2S,3S)-1,2-Epoxy-3-(Cbz-amino)-4-phenylbutane → benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamate

HRID 501689Notes

Reaction equation

HRID 501689 reaction equation
Cl([O-])(=O)(=O)=O.[Li+].[CH2:7]([O:10][C@H:11]1[C:19]2[C:14](=[CH:15][C:16]([O:20][CH3:21])=[CH:17][CH:18]=2)[C@@H:13]([NH2:22])[CH2:12]1)[CH:8]=[CH2:9].[O:23]1[CH2:25][C@@H:24]1[C@@H:26]([NH:34][C:35](=[O:44])[O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[Cl-].[Na+].O.C([O-])(O)=O.[Na+]>CC#N>[CH2:7]([O:10][C@H:11]1[C:19]2[C:14](=[CH:15][C:16]([O:20][CH3:21])=[CH:17][CH:18]=2)[C@@H:13]([NH:22][CH2:25][C@@H:24]([OH:23])[C@@H:26]([NH:34][C:35](=[O:44])[O:36][CH2:37][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:12]1)[CH:8]=[CH2:9]

Participants

6

Reactant 4

HCID 9861019(2S,3S)-1,2-Epoxy-3-(Cbz-amino)-4-phenylbutaneHCID 23665649Lithium perchlorateHCID 59676150(1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-amineHCID 129703874Sodium hydrogencarbonate brine

Product 1

HCID 59676147benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamateYield 39%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

Step V (1): Lithium perchlorate (838 mg, 7.88 mmol) was added to a solution of (1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-amine (765 mg, 3.49 mmol, from Step U(2)) and benzyl (S)-1-((S)-oxiran-2-yl)-2-phenylethyl-carbamate (1.04 g, 3.49 mmol) in CH3CN (50 mL). The reaction mixture was stirred at 50° C. for 36 h. The reaction mixture was poured into brine/NaHCO3 solution. Extracted with EtOAc, washed combined extracts with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (1-10% MeOH (with 0.1% triethylamine)/chloroform, linear gradient) to give 700 mg (39% yield) of benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamate. LC-MS (M+H)+=517.06; HRMS (M+H)+=517.2700; [α]D +14.45 (c=6.50 mg/mL, dichloroethane); 1H NMR (500 MHz, CDCl3) δ ppm 1.59 (s, 3H) 1.82-1.93 (m, 1H) 2.58-2.75 (m, 2H) 2.80-2.93 (m, 2H) 2.97-3.07 (m, 1H) 3.44-3.54 (m, 1H) 3.78 (s, 3H) 3.88 (t, 1H) 4.09 (t, J=5.19 Hz, 2H) 4.76 (s, 1H) 4.84-4.94 (m, 1H) 5.02 (s, 2H) 5.18 (d, J=10.38 Hz, 1H) 5.31 (dd, J=17.24, 1.37 Hz, 1H) 5.89-6.01 (m, 1H) 6.79-6.92 (m, 2H) 7.14-7.37 (m, 11H).

Workup

  1. extractionExtracted with EtOAc
  2. washwashed
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (1-10% MeOH (with 0.1% triethylamine)/chloroform, linear gradient)

Sources & evidence

ORD record
ord-933658f3a08049398497f79cf239bf64
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

Loading…