Iodoethane → (3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclobutyl-ethoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine

HRID 2075085Notes

Reaction equation

HRID 2075085 reaction equation
[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[CH:25]([CH:27]1[CH2:30][CH2:29][CH2:28]1)[OH:26])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[H-].[Na+].[CH2:42](I)[CH3:43]>C1COCC1>[F:39][C:2]([F:1])([F:38])[C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:33]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[CH:25]([CH:27]1[CH2:28][CH2:29][CH2:30]1)[O:26][CH2:42][CH3:43])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

Participants

5

Reactant 3

HCID 6340Iodoethane2×HCID 24758Sodium hydride2×HCID 589686942-{[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl-cyclobutyl-methanol

Product 1

HCID 58968657(3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclobutyl-ethoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amineYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-cyclobutyl-methanol (23 mg; 0.041 mmol) in THF (1.5 mL) at 0° C. was added sodium hydride (15 mg; 0.375 mmol; 60% dispersion in mineral oil). After stirring at room temperature for 30 minutes ethyl iodide (0.05 mL; 0.625 mmol) was added. Reaction was stirred for 2 hours. More sodium hydride (15 mg; 0.375 mmol; 60% dispersion in mineral oil) and iodoethane (0.05 mL; 0.625 mmol) were added. Reaction stirred for 72 hours. Reaction was quenched with 2 drops of water. The reaction was filtered over a 1 g Bakerbond silica cartridge (Mallinkrodt Baker Inc. Phillipsburg, N.J.) (eluted with ethyl acetate). The crude was purified by RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 5-30% ethyl acetate in heptane) to give 21 mg (87% yield) of a gum. MS (ES+): Calc: 595.5, Found: 596.4 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 7.78 (s, 1H), 7.65 (s, 2H), 7.53 (s, 2H), 7.33 (s, 1H), 4.83 (q, J=16.18 Hz, 2H), 4.73 (q, J=16.18, 14.11 Hz, 2H), 4.42 (d, J=6.64 Hz, 1H), 4.22 (s, 3H), 3.20 (m, J=7.05, 6.64 Hz, 2H), 2.49 (m, J=7.88, 7.05 Hz, 1H), 2.07-1.57 (m, 6H), 1.11 (t, J=7.05 Hz, 3H).

Workup

  1. additionwas added
  2. customReaction
  3. customReaction
  4. stirringstirred for 72 hours
  5. customReaction
  6. customwas quenched with 2 drops of water
  7. filtrationThe reaction was filtered over a 1 g Bakerbond silica cartridge (Mallinkrodt Baker Inc. Phillipsburg, N.J.) (eluted with ethyl acetate)
  8. customThe crude was purified by RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 5-30% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-6add6630e0854b80839b05d197bb0d34
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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