Tetrahydrofuran → methyl 6-iodo-5-(2-(1-trityl-1H-imidazol-2-yl)ethoxy)nicotinate

HRID 1799832Notes

Reaction equation

HRID 1799832 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[C:15]([N:34]1[CH:38]=[CH:37][N:36]=[C:35]1[CH2:39][CH2:40][OH:41])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O[C:43]1[C:44]([I:53])=[N:45][CH:46]=[C:47]([CH:52]=1)[C:48]([O:50][CH3:51])=[O:49].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCCC1>O>[I:53][C:44]1[C:43]([O:41][CH2:40][CH2:39][C:35]2[N:34]([C:15]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:38]=[CH:37][N:36]=2)=[CH:52][C:47]([C:48]([O:50][CH3:51])=[O:49])=[CH:46][N:45]=1

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 221201462-(1-trityl-1H-imidazol-2-yl)ethanolHCID 57900098Methyl 5-hydroxy-6-iodopyridine-3-carboxylate

Product 1

HCID 58204676methyl 6-iodo-5-(2-(1-trityl-1H-imidazol-2-yl)ethoxy)nicotinateYield 44%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Diisopropyl azodicarboxylate (1160 uL, 5.90 mmol) was added dropwise to a mixture of 2-(1-trityl-1H-imidazol-2-yl)ethanol (1900 mg, 5.4 mmol), methyl 5-hydroxy-6-iodonicotinate (1570 mg, 5.63 mmol) and Triphenylphosphine (1550 mg, 5.90 mmol) in Tetrahydrofuran (45.0 mL, 555 mmol) at 0° C. After stirring for 3 hours the mixture was mixed with water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over MgSO4 and concentrated in vacuum. The residue was purified on 40 g silica column eluting with 50% ethyl acetate in DCM to give 1.45 g (44%) of methyl 6-iodo-5-(2-(1-trityl-1H-imidazol-2-yl)ethoxy)nicotinate. MS (ESI+): 616.0. 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J=1.9, 1H), 7.40-7.28 (m, 10H), 7.20-7.16 (m, 6H), 6.99 (d, J=1.5, 1H), 6.81 (d, J=1.5, 1H), 3.98-3.91 (m, 5H), 2.46 (t, J=7.3, 2H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuum
  5. customThe residue was purified on 40 g silica column
  6. washeluting with 50% ethyl acetate in DCM

Sources & evidence

ORD record
ord-d6520c0749f34d2e8ea15b29e1a79ac7
Source dataset
uspto-grants-2013_01
Patent number
US08343955B2

Reaction notes

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