Triphenylphosphine → Methyl 6-(tert-butoxycarbonyl(4,4,4-trifluoro-1-(4'-(trifluoromethyl)biphenyl-4-yl)butyl)amino)nicotinate

HRID 1427509Notes

Reaction equation

HRID 1427509 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[F:15][C:16]([F:38])([F:37])[CH2:17][CH2:18][CH:19]([C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)O.[C:39]([O:43][C:44]([NH:46][C:47]1[CH:56]=[CH:55][C:50]([C:51]([O:53][CH3:54])=[O:52])=[CH:49][N:48]=1)=[O:45])([CH3:42])([CH3:41])[CH3:40].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:39]([O:43][C:44]([N:46]([CH:19]([C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)[CH2:18][CH2:17][C:16]([F:38])([F:37])[F:15])[C:47]1[CH:56]=[CH:55][C:50]([C:51]([O:53][CH3:54])=[O:52])=[CH:49][N:48]=1)=[O:45])([CH3:42])([CH3:40])[CH3:41]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 2764194Methyl 6-((tert-butoxycarbonyl)amino)nicotinateHCID 866673024,4,4-Trifluoro-1-(4'-(trifluoromethyl)biphenyl-4-yl)butan-1-ol

Product 1

HCID 86667303Methyl 6-(tert-butoxycarbonyl(4,4,4-trifluoro-1-(4'-(trifluoromethyl)biphenyl-4-yl)butyl)amino)nicotinateYield 21.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diisopropyl azodicarboxylate (50 μL, 0.25 mmol) was added to a room temperature solution of 4,4,4-trifluoro-1-(4′-(trifluoromethyl)biphenyl-4-yl)butan-1-ol (84 mg, 0.24 mmol), methyl 6-(tert-butoxycarbonylamino)nicotinate (74 mg, 0.29 mmol), and triphenylphosphine (65 mg, 0.25 mmol) in 1.5 mL THF. The resulting solution was stirred overnight at room temperature. The solution was partitioned between dichloromethane and water. The organic layer was dried over MgSO4 and concentrated to give a colorless solid. Purification by silica gel chromatography provided methyl 6-(tert-butoxycarbonyl(4,4,4-trifluoro-1-(4′-(trifluoromethyl)biphenyl-4-yl)butyl)amino)nicotinate (30 mg, 21%) as a colorless solid. 1H NMR (400 MHz, CDCl3) δ 8.99-9.01 (m, 1H), 8.17-8.21 (m, 1H), 7.63-7.69 (m, 4H), 7.49-7.54 (m, 3H), 7.39-7.44 (m, 2H), 5.98-6.08 (m, 1H), 3.92 (s, 3H), 2.61-2.74 (m, 1H), 2.39-2.54 (m, 1H), 2.17-2.36 (m, 2H), 1.31 (s, 9H).

Workup

  1. customThe solution was partitioned between dichloromethane and water
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated
  4. customto give a colorless solid
  5. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-6aa27e755e924972ad72db1b19e6de8b
Source dataset
uspto-grants-2015_01
Patent number
US08933104B2

Reaction notes

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