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 1994511Notes

Reaction equation

HRID 1994511 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 μL). 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)bi phenyl-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-587ad4b6fc29420880789d031309ff91
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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