Ammonium Chloride → HCID 22663418, compound

HRID 380399Notes

Reaction equation

HRID 380399 reaction equation
Br[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[CH3:21][O:22][C:23]1[C:28]2[N:29]=[C:30]([CH2:32][O:33][CH3:34])[NH:31][C:27]=2[C:26]([C:35](ON2C3C=CC=CC=3N=N2)=[O:36])=[CH:25][CH:24]=1.[Cl-].[NH4+]>O1CCCC1.CCCCCC>[Cl:15][C:11]1[CH:10]=[C:9]([CH:14]=[CH:13][CH:12]=1)[O:8][C:3]1[C:2]([C:35]([C:26]2[C:27]3[N:31]=[C:30]([CH2:32][O:33][CH3:34])[NH:29][C:28]=3[C:23]([O:22][CH3:21])=[CH:24][CH:25]=2)=[O:36])=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 22663367HCID 22663367, compoundHCID 178418339ButyllithiumHCID 178494655HCID 178494655, compound

Product 1

HCID 22663418HCID 22663418, compoundYield 18.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

A solution of 3-bromo-2-(3-chlorophenoxy)pyridine (0.43 g, Reference Example 16) in dry tetrahydrofuran (6 ml), at −70° C., was treated with butyl lithium in hexane (0.64 ml, 2.5M). The mixture was then stirred at −70° C. for 45 minutes then treated with a solution of 1-benzotriazolyl 7-methoxy-2-methoxymethyl-3H-benzimidazole-4-carboxylate [0.177 g, Reference Example 1(a)] in dry tetrahydrofuran (2 ml) and stirring was continued at −70° C. for 10 minutes. The reaction mixture was allowed to warm to room temperature, then stirred at this temperature for 2 hours, then treated with aqueous ammonium chloride solution, and then extracted with ethyl acetate (20 ml). The organic extract was dried and concentrated to give a brown syrup which was purified by flash chromatography on silica eluting initially with a mixture of diethyl ether and pentane (1:1, v/v), then with a mixture of diethyl ether and pentane (7:3, v/v) and then with diethyl ether to give the title compound (0.04 g) as white solid, m.p. 181-183° C. [Elemental analysis:—C,62.17, H,4.32, N,10.15%. Calculated:—C,62.35, H,4.28, N,9.91%]. NMR (CDCl3):—δ 3.52(s,3H), 4.13(s,3H), 4.85(s,2H), 6.73(d,J=8 Hz,1H), 7.00(m,1H), 7.12(t,J=2 Hz,1H), 7.16(m,1H), 7.2(dd,J=7 Hz,J=5 Hz,1H), 7.28(t,J=8 Hz,1H), 7.55(d,J=8 Hz,1H), 7.85(dd,J=8 Hz,J=2 Hz,1H), 8.83(dd,J=4 Hz,J=1 Hz,1H).

Workup

  1. stirringstirring
  2. waitwas continued at −70° C. for 10 minutes
  3. temperatureto warm to room temperature
  4. stirringstirred at this temperature for 2 hours
  5. extractionextracted with ethyl acetate (20 ml)
  6. extractionThe organic extract
  7. customwas dried
  8. concentrationconcentrated
  9. customto give a brown syrup which
  10. customwas purified by flash chromatography on silica eluting initially with a mixture of diethyl ether and pentane (1:1
  11. additionv/v), then with a mixture of diethyl ether and pentane (7:3

Sources & evidence

ORD record
ord-6d9b499134a440139782f44b201df4ef
Source dataset
uspto-grants-2001_10
Patent number
US06303600B1

Reaction notes

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