Trifluoroacetic acid → (1R,2S)-1-azido-1-[3,5-bis(trifluoromethyl)phenyl]-N-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)bi phenyl-2-yl]methyl}propan-2-amine

HRID 1028540Notes

Reaction equation

HRID 1028540 reaction equation
C(OC(=O)[N:7]([C@@H:30]([CH3:49])[C@H:31]([N:46]=[N+:47]=[N-:48])[C:32]1[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[C:34]([C:42]([F:45])([F:44])[F:43])[CH:33]=1)[CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:24]=[C:23]([CH:25]([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=1[O:28][CH3:29])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:46]([C@H:31]([C:32]1[CH:33]=[C:34]([C:42]([F:43])([F:44])[F:45])[CH:35]=[C:36]([C:38]([F:39])([F:40])[F:41])[CH:37]=1)[C@@H:30]([NH:7][CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:17])([F:18])[F:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:24]=[C:23]([CH:25]([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=1[O:28][CH3:29])[CH3:49])=[N+:47]=[N-:48]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86603415tert-butyl{(1S,2R)-2-azido-2-[3,5-bis(trifluoromethyl)phenyl]-1-methylethyl}{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

Product 1

HCID 86603414(1R,2S)-1-azido-1-[3,5-bis(trifluoromethyl)phenyl]-N-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)bi phenyl-2-yl]methyl}propan-2-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl{(1S,2R)-2-azido-2-[3,5-bis(trifluoromethyl)phenyl]-1-methylethyl}{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (21.7 mg, 0.030 mmol) in CH2Cl2 (2 mL) was added TFA (200 mL). The reaction was stirred at room temperature for 1 hour and then diluted with CH2Cl2 (25 mL). The CH2Cl2 solution was washed with 1 N NaOH (15 mL) and the aqueous phase was re-extracted with CH2Cl2 (25 mL). The organic extracts were combined, washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 15% EtOAc/hexanes afforded (1R,2S)-1-azido-1-[3,5-bis(trifluoromethyl)phenyl]-N-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}propan-2-amine. Rf=0.45 (15% EtOAc/hexanes). LCMS=619.2 (M+1)+.

Workup

  1. washThe CH2Cl2 solution was washed with 1 N NaOH (15 mL)
  2. extractionthe aqueous phase was re-extracted with CH2Cl2 (25 mL)
  3. washwashed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the residue by flash chromatography with 15% EtOAc/hexanes

Sources & evidence

ORD record
ord-08bbeccfac3f4141bdbef96f7773e733
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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