Potassium Carbonate → (1S,2S)-2-amino-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol

HRID 132939Notes

Reaction equation

HRID 132939 reaction equation
FC1C=C(C=C(F)C=1)C[C@H]1[C@@H]([C@H]2C[C@@H](OCC=C)CN2C(OC(C)(C)C)=O)OC(=O)N1.[F:32][C:33]1[CH:34]=[C:35]([CH:62]=[C:63]([F:65])[CH:64]=1)[CH2:36][C@H:37]1[C@@H:41]([C@H:42]2[CH2:47][CH2:46][CH2:45][CH2:44][N:43]2[CH:48]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[O:40]C(=O)[NH:38]1.FC1C=C(C=C(F)C=1)C[C@@H]([C@@H]([C@H]1C[C@@H](OCC=C)CN1C(OC(C)(C)C)=O)O)C(O)=O.C(=O)([O-])[O-].[K+].[K+].BrC(C1C=CC=CC=1)C1C=CC=CC=1>C(#N)C>[NH2:38][C@@H:37]([CH2:36][C:35]1[CH:62]=[C:63]([F:65])[CH:64]=[C:33]([F:32])[CH:34]=1)[C@@H:41]([C@H:42]1[CH2:47][CH2:46][CH2:45][CH2:44][N:43]1[CH:48]([C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1)[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[OH:40]

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 236603BromodiphenylmethaneHCID 67315782(2R,4R)-tert-butyl 2-((4S,5S)-4-(3,5-difluorobenzyl)-2-oxooxazolidin-5-yl)-4-(allyloxy)pyrrolidine-1-carboxylateHCID 67316915(2S,3S)-2-(3,5-difluorobenzyl)-3-((2R,4R)-4-(allyloxy)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-3-hydroxypropanoic acidHCID 69195572(4S,5S)-4-(3,5-difluorobenzyl)-5-((R)-1-benzhydrylpiperidin-2-yl)oxazolidin-2-one

Product 1

HCID 58608199(1S,2S)-2-amino-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)propan-1-olYield 50%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

Step I (7): Preparation of (4S,5S)-4-(3,5-difluorobenzyl)-5-((R)-1-benzhydrylpiperidin-2-yl)oxazolidin-2-one. To a solution of (4S,5R)-4-(3,5-difluorobenzyl)-5-((R)-piperidin-2-yl)oxazolidin-2-one (Step I (6), 70 mg, 0.24 mmol) in acetonitrile (1.8 mL) were added potassium carbonate (50 mg, 0.36 mmol) and bromodiphenylmethane (90 mg, 0.36 mmol). The reaction mixture was then heated to 100° C. for 30 min using microwave heating. The solvent was removed and the crude mixture was purified by silica gel Flash Chromatography to give 60 mg of the title compound (50% yield): 1H NMR (CDCl3, 500 MHz) δ 1.28 (1H, brd s), 1.56-1.83 (4H, m), 1.94 (1H, m), 2.13 (1H, t, J=10 Hz), 2.67 (1H, m), 2.77 (1H, m), 2.88 (1H, m), 3.16 (1H, t, J=5 Hz), 3.81 (1H, m), 4.95 (1H, s), 5.10 (1H, s), 5.14 (1H, m), 6.54 (2H, m), 6.69 (1H, m), 7.18-7.27 (4H, m), 7.32-7.38 (4H, m), 7.42 (2H, d, J=10 Hz). MS (ESI) (M+Na)+ 485.12.

Workup

  1. temperatureheating
  2. customThe solvent was removed
  3. customthe crude mixture was purified by silica gel Flash Chromatography

Sources & evidence

ORD record
ord-d7c8cea54a114143ac46c23a900c790b
Source dataset
uspto-grants-2008_06
Patent number
US07388007B2

Reaction notes

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