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

HRID 501690Notes

Reaction equation

HRID 501690 reaction equation
[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:38])[C@@H:19]([NH:27]C(=O)OCC2C=CC=CC=2)[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:6]1)[CH:2]=[CH2:3]>COCCOC.O>[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:38])[C@@H:19]([NH2:27])[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:6]1)[CH:2]=[CH2:3]

Participants

3

Reactant 1

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

Product 1

HCID 59676157(2R,3S)-1-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-amino-4-phenylbutan-2-olYield 49%

Reagents, catalysts & solvents 1

HCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

Step V (2): A mixture of benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamate (700 mg, 1.36 mmol, from step N(1)), Ba(OH)2.H2O (1.46 g, 7.72 mmol), and DME/H2O (18 mL/12 mL) was heated at 110° C. in a sealed tube. After 16 h, cooled to rt, filtered of solid. Rinsed the vessel and filtercake with fresh DME and concentrated the filtrate in vacuo. The crude product was purified by silica-gel column chromatography (1-20% MeOH (containing 0.1% triethylamine)/chloroform, linear gradient) to provide 255 mg (49% yield) of the title compound. LC-MS (M+H)=383.0; HRMS (M+H)+=383.2332; [α]D +29.84 (c=6.43 mg/mL, methanol); 1H NMR (500 MHz, CDCl3) δ ppm 1.67 (d, 4H) 1.97 (d, J=13.43 Hz, 1H) 2.43-2.54 (m, 1H) 2.60-2.71 (m, 1H) 2.81 (dd, J=11.90, 8.55 Hz, 1H) 2.90-3.05 (m, 2H) 3.10-3.18 (m, 1H) 3.47 (s, 1H) 3.57 (s, 1H) 3.81 (s, 3H) 4.02-4.16 (m, 2H) 4.77 (dd, J=6.10, 3.97 Hz, 1H) 5.18 (dd, J=10.38, 1.53 Hz, 1H) 5.31 (dd, J=17.24, 1.68 Hz, 1H) 5.96 (dd, 1H) 6.85 (dd, J=8.24, 2.44 Hz, 1H) 6.95 (d, J=2.14 Hz, 1H) 7.15-7.35 (m, 6H).

Workup

  1. temperaturecooled to rt
  2. filtrationfiltered of solid
  3. washRinsed the vessel and filtercake with fresh DME
  4. concentrationconcentrated the filtrate in vacuo
  5. customThe crude product was purified by silica-gel column chromatography (1-20% MeOH (containing 0.1% triethylamine)/chloroform, linear gradient)

Sources & evidence

ORD record
ord-334efe465f3843afbd6bc462b6a03a48
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

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