Ammonium Chloride → HCID 178495100, compound

HRID 275574Notes

Reaction equation

HRID 275574 reaction equation
C([N-]C(C)C)(C)C.[Li+].[PH:9](=[O:12])([OH:11])[OH:10].[CH2:13]([C:15](CC)([CH:17]([O:42][CH3:43])[C:18]1[N:22]=[CH:21][N:20]([C:23]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:19]=1)C)C.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:56])(=O)=O)=CC=1.[Cl-].[NH4+]>O1CCCC1>[PH:9](=[O:10])([OH:12])[OH:11].[F:56][CH2:13][CH2:15][CH:17]([O:42][CH3:43])[C:18]1[N:22]=[CH:21][N:20]([C:23]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:19]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 588007N-FluorobenzenesulfonimideHCID 2724682Lithium diisopropylamideHCID 178444084HCID 178444084, compound

Product 1

HCID 178495100HCID 178495100, compoundYield 34.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of lithium diisopropylamide (1.75 ml, 1.5M in cyclohexane) was added dropwise, with stirring, to a solution of diethyl 3-methoxy-3(1-trityl-1,2,4-triazol-3-yl)propane phosphonate (0.65 g, prepared as described in Example 25) in dry tetrahydrofuran (15 ml), under nitrogen and with temperature maintained below -60° C. After a further twenty minutes, a solution of N-fluorobenzenesulphonimide (0.51 g) in tetrahydrofuran (15 ml) was added dropwise to the stirred reaction mixture at below -60° C. The mixture was stirred for a further two hours at -78° C., allowed to warm to room temperature and to stand overnight. It was then poured into saturated ammonium chloride solution and extracted with ethyl acetate. The extracts were washed with brine, dried over magnesium sulphate and evaporated under reduced pressure. The residue was chromatographed on silica, using dichloromethane-ethanol (49:1) as eluant, to give diethyl (1RS,3RS; 1RS,3SR)-1-fluoro-3-methoxy-3(1-trityl-1,2,4--triazol-3-yl)propane phosphonate (0.21 g) as an oily mixture of diastereoisomers in a ratio of 3:1 or 1:3. NMR (CDCl3): δ1.3(6H,2t), 2.5-2.7(2H,m), 3.3(3H,2xs), 4.2(4H,m), 4.6-4.8(2H,m), 7.1-7.3(15H,m), 8.0(1H,2xs). M/S: M+ 537. The structures were confirmed by 19F and 13C NMR.

Workup

  1. temperaturemaintained below -60° C
  2. waitAfter a further twenty minutes
  3. temperatureto warm to room temperature
  4. waitto stand overnight
  5. extractionextracted with ethyl acetate
  6. washThe extracts were washed with brine
  7. dry with materialdried over magnesium sulphate
  8. customevaporated under reduced pressure
  9. customThe residue was chromatographed on silica

Sources & evidence

ORD record
ord-9dff284523994bd981b14d35481624b2
Source dataset
uspto-grants-1995_02
Patent number
US05393732

Reaction notes

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