Water → HCID 15230643, compound

HRID 2379474Notes

Reaction equation

HRID 2379474 reaction equation
[C:1]1([NH:7][C:8]2[N:9]=[N:10][N:11]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[N:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.[F:33][C:34]1[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=1[N:41]=[C:42]=[O:43].O>O1CCCC1>[F:33][C:34]1[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=1[NH:41][C:42](=[O:43])[N:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:8]1[N:9]=[N:10][N:11]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[N:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 5932582,4-Difluorophenyl isocyanateHCID 18957150HCID 18957150, compoundHCID 178418339Butyllithium

Product 1

HCID 15230643HCID 15230643, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred, cold (-78° C.) solution of (±)N-phenyl-2-[8-[(tetrahydro-2H-pyran-2-yl) oxy]octyl]-2H-tetrazol-5-amine (0.6161 9, 0.001650 mol) in anhydrous tetrahydrofuran (20 mL) was added a 1.6M solution of n-butyl lithium in hexanes (1.0 mL, 0.0016 mol) under a nitrogen atmosphere, and the mixture was stirred. After 2.5 hours, 2,4-difluorophenyl isocyanate (0. 195 mL, 0. 00165 mol) was added dropwise, and the mixture was stirred. After 3 hours the mixture was allowed to warm to room temperature and then stirred 1.5 days. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride, dried (Na2SO4), and rotoevaporated to an oil. The oil was chromatographed on silica gel (120 g, 230-400 mesh) using chloroform-diethyl ether (24:1, 13×100 mL) as eluent. Fractions containing product were rotoevaporated from diethyl ether to give the title compound as a yellow oil. The oil was dried in vacuo, yield 0.5406 g (64%). 1H NMR (CDC13): δ 10.4 (br s, 1H), 8.3 (m, 1H), 7.5 (m, 3H), 7.4 (d, 2H), 6.9 (m, 2H), 4.6 (m, 1H), 4.5 (t, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.5 (m, 1H), 3.4 (m, 1H), 2.0 (m, 2H), 1.5-1.9 (m, 9H), 1.3 (m, 7H).

Workup

  1. stirringthe mixture was stirred
  2. waitAfter 3 hours the mixture was allowed
  3. stirringstirred 1.5 days
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with saturated sodium chloride
  6. dry with materialdried (Na2SO4)
  7. customThe oil was chromatographed on silica gel (120 g, 230-400 mesh)
  8. additionFractions containing product

Sources & evidence

ORD record
ord-6363ded67d9441b9a6df514e492aae61
Source dataset
uspto-grants-1994_11
Patent number
US05362744

Reaction notes

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