Sodium Bicarbonate → benzyl (2S,3R)-4-((R)-2-(allyloxy)-1-phenylethylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate

HRID 501681Notes

Reaction equation

HRID 501681 reaction equation
Cl([O-])(=O)(=O)=O.[Li+].[CH2:7]([O:10][CH2:11][C@@H:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[NH2:13])[CH:8]=[CH2:9].[F:20][C:21]1[CH:22]=[C:23]([CH2:28][C@H:29]([NH:33][C:34](=[O:43])[O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@H:30]2[CH2:32][O:31]2)[CH:24]=[C:25]([F:27])[CH:26]=1.C([O-])(O)=O.[Na+]>CC#N.[Cl-].[Na+].O>[CH2:7]([O:10][CH2:11][C@H:12]([NH:13][CH2:32][C@@H:30]([OH:31])[C@@H:29]([NH:33][C:34](=[O:43])[O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH2:28][C:23]1[CH:22]=[C:21]([F:20])[CH:26]=[C:25]([F:27])[CH:24]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH:8]=[CH2:9]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 10131699HCID 10131699, compoundHCID 23665649Lithium perchlorateHCID 68465142(1R)-2-Allyloxy-1-phenyl-ethanamine

Product 1

HCID 86622319benzyl (2S,3R)-4-((R)-2-(allyloxy)-1-phenylethylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamateYield 72.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

Step Q (4): Lithium perchlorate (1.59 g, 15 mmol) was added to a solution of (R)-2-(allyloxy)-1-phenylethanamine (530 mg, 2.99 mmol) from Step Q (3) and benzyl (S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethylcarbamate (996 mg, 2.99 mmol) in CH3CN (10 mL). The resulting mixture was stirred at 50° C. for 16 h, then poured into a solution of brine and saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography to give 1.1 g (72% yield) of benzyl (2S,3R)-4-((R)-2-(allyloxy)-1-phenylethylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate. LC-MS (M+H)+=511.5; 1H NMR (300 MHz, CDCl3) δ ppm 2.36-2.53 (m, J=10.98 Hz, 1H) 2.55-3.00 (m, 3H) 3.25-3.74 (m, 3H) 3.77-4.19 (m, 3H) 4.71-4.84 (m, 1H) 5.00 (s, 2H) 5.09-5.37 (m, 2H) 5.74-6.00 (m, 1H) 6.50-6.78 (m, 3H) 7.16-7.42 (m, 10H).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. customdried
  4. dry with materialover dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0c74db48221a4cb89be879e6678fcbd9
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

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