Sodium Bicarbonate → tert-butyl (2S,3R)-4-(3-(allyloxy)-1-(3-methoxyphenyl)propylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamate

HRID 501685Notes

Reaction equation

HRID 501685 reaction equation
Cl([O-])(=O)(=O)=O.[Li+].[CH2:7]([O:10][CH2:11][CH2:12][CH:13]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=1)[NH2:14])[CH:8]=[CH2:9].[O:23]1[CH2:25][C@@H:24]1[C@@H:26]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C([O-])(O)=O.[Na+]>CC#N.[Cl-].[Na+].O>[CH2:7]([O:10][CH2:11][CH2:12][CH:13]([NH:14][CH2:25][C@@H:24]([OH:23])[C@@H:26]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:39])([CH3:38])[CH3:40])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=1)[CH:8]=[CH2:9]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 9903372(2S,3S)-(-)-3-tert-Butoxycarbonylamino-1,2-epoxy-4-phenylbutaneHCID 23665649Lithium perchlorateHCID 684659353-(Allyloxy)-1-(3-methoxyphenyl)propan-1-amine

Product 1

HCID 86622322tert-butyl (2S,3R)-4-(3-(allyloxy)-1-(3-methoxyphenyl)propylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamateYield 82.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

Step R (4): Lithium perchlorate (936 mg, 8.80 mmol) was added to a mixture of 3-(allyloxy)-1-(3-methoxyphenyl)propan-1-amine (390 mg, 1.76 mmol) from Step R(3) and tert-butyl (S)-1-((S)-oxiran-2-yl)-2-phenylethylcarbamate (464 mg, 1.76 mmol) from Aldrich, dissolved in CH3CN (10 mL). The resulting mixture was heated at 50° C. for 16 h. The reaction mixture was poured into a mixture of brine and saturated aqueous NaHCO3 solution. Extracted with EtOAc, washed combined extracts with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography to give 700 mg (quantitative yield) of tert-butyl (2S,3R)-4-(3-(allyloxy)-1-(3-methoxyphenyl)propylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamate as a mixture of two diastereomers. LC-MS (M+H)+=485.57; 1H NMR (300 MHz, CDCl3) δ ppm 1.14-1.43 (m, 9H) 2.56-3.04 (m, 4H) 3.24-3.38 (m, 1H) 3.39-3.58 (m, 2H) 3.69-4.01 (m, 7H) 4.60 (t, J=9.88 Hz, 1H) 5.04-5.30 (m, 2H) 5.72-5.99 (m, 1H) 6.73-7.00 (m, 2H) 7.09-7.33 (m, 7H).

Workup

  1. extractionExtracted with EtOAc
  2. washwashed
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-af4f11129a4e4d6cb5ed6d73ede4a921
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

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