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

HRID 132938Notes

Reaction equation

HRID 132938 reaction equation
F[C:2]1[CH:3]=[C:4]([CH:28]=[C:29](F)[CH:30]=1)[CH2:5][C@@H:6]([C@@H:10]([C@H:12]1[CH2:16][C@@H:15](OCC=C)[CH2:14]N1C(OC(C)(C)C)=O)O)C(O)=O.[F:32][C:33]1[CH:34]=[C:35]([CH:49]=[C:50]([F:52])[CH:51]=1)[CH2:36][C@H:37]1[C@@H:41]([C@H:42]2[CH2:47][CH2:46][CH2:45][CH2:44][NH:43]2)[O:40]C(=O)[NH:38]1.FC1C=C(C=C(F)C=1)C[C@H](C(N1[C@@H](CC2C=CC=CC=2)COC1=O)=O)[C@@H]([C@H]1C[C@@H](OCC=C)CN1C(OC(C)(C)C)=O)O.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:38][C@@H:37]([CH2:36][C:35]1[CH:34]=[C:33]([F:32])[CH:51]=[C:50]([F:52])[CH:49]=1)[C@@H:41]([C@H:42]1[CH2:47][CH2:46][CH2:45][CH2:44][N:43]1[CH:5]([C:4]1[CH:3]=[CH:2][CH:30]=[CH:29][CH:28]=1)[C:6]1[CH:10]=[CH:12][CH:16]=[CH:15][CH:14]=1)[OH:40]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 67316359(2R,4R)-tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)-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 69195213(4S,5R)-4-(3,5-difluorobenzyl)-5-((R)-piperidin-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-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Step I (6): Preparation of (4S,5R)-4-(3,5-difluorobenzyl)-5-((R)-piperidin-2-yl)oxazolidin-2-one. A solution of (R)-tert-butyl 2-((4S,5S)-4-(3,5-difluorobenzyl)-2-oxooxazolidin-5-yl)piperidine-1-carboxylate (Step I (5), 200 mg) in CH2Cl2 (4 mL) was treated with TFA (2 mL). This reaction mixture was stirred at rt for 1 h. The mixture was then concentrated in vacuo with addition of toluene. 1N HCl solution (50 mL) was added and the mixture was extracted with diethyl ether, neutralized with 50% aqueous NaOH to pH=12. The mixture was extracted with ethyl acetate (50 mL) twice. The combined organic layers were dried (Na2SO4), and concentrated in vacuo to give 132 mg of the title compound:

Workup

  1. concentrationThe mixture was then concentrated in vacuo with addition of toluene
  2. addition1N HCl solution (50 mL) was added
  3. extractionthe mixture was extracted with diethyl ether
  4. extractionThe mixture was extracted with ethyl acetate (50 mL) twice
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9edef0d70569471089261bcc9f512475
Source dataset
uspto-grants-2008_06
Patent number
US07388007B2

Reaction notes

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