Tetrahydrofuran → 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

HRID 1994510Notes

Reaction equation

HRID 1994510 reaction equation
C1(P([N:15]=[N+:16]=[N-:17])(C2C=CC=CC=2)=O)C=CC=CC=1.[C:18]([O:22][C:23](=[O:65])[N:24]([C@@H:47]([CH3:64])[C@H:48]([C:50]1[CH:55]=[C:54]([C:56]([F:59])([F:58])[F:57])[CH:53]=[C:52]([C:60]([F:63])([F:62])[F:61])[CH:51]=1)O)[CH2:25][C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=1C1C=C(C(C)C)C=CC=1OC)([CH3:21])([CH3:20])[CH3:19].C1C=CC(P([C:79]2[CH:84]=[CH:83][CH:82]=[CH:81]C=2)C2C=CC=CC=2)=CC=1.N(C(OCC)=O)=N[C:87](OCC)=O.[CH2:97]1[CH2:101][O:100][CH2:99][CH2:98]1>CCOC(C)=O>[C:18]([O:22][C:23](=[O:65])[N:24]([C@@H:47]([CH3:64])[C@H:48]([N:15]=[N+:16]=[N-:17])[C:50]1[CH:51]=[C:52]([C:60]([F:62])([F:61])[F:63])[CH:53]=[C:54]([C:56]([F:57])([F:58])[F:59])[CH:55]=1)[CH2:25][C:26]1[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[CH:28][C:27]=1[C:97]1[CH:98]=[C:83]([CH:82]([CH3:81])[CH3:87])[CH:84]=[CH:79][C:101]=1[O:100][CH3:99])([CH3:19])([CH3:20])[CH3:21]

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 11776Triphenylphosphine2×HCID 199401P,P-Diphenylphosphinic azide2×HCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 87121496Tert-butyl{(1s,2s)-2-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-1-methylethyl}{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A dry flask was charged with THF (1 mL) diethyl azodicarboxylate (DEAD) (11 μL, 0.0698 mmol) and diphenylphosphoryl azide (DPPA) (15 μL, 0.0698 mmol). tert-butyl{(1S,2S)-2-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-1-methylethyl}{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (20.7 mg, 0.0698 mmol) was added by cannula in THF (1 mL). Next Ph3P (18.3 mg, 0.0698 mmol) was added. The reaction was stirred at room temperature for 30 min, and then additional DEAD (11 μL, 0.0698 mmol), DPPA (15 μL, 0.0698 mmol), and Ph3P (18.3 mg, 0.0698 mmol) were added. After an additional 30 min, the reaction was diluted with EtOAc (40 mL) and washed with water and brine (15 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 15% EtOAc/hexanes afforded 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. Rf=0.60 (25% EtOAc/hexanes). LCMS=619.3 (M+1−BOC)+.

Workup

  1. waitAfter an additional 30 min
  2. washwashed with water and brine (15 mL each)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography with 15% EtOAc/hexanes

Sources & evidence

ORD record
ord-55052fbf903543fca87f9601c5f2451b
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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