Lithium diisopropylamide → Dihydro-7-(2-acetylthioethyl)-1-pyrindine-6,6-bisphosphonic acid, tetraethyl ester

HRID 963641Notes

Reaction equation

HRID 963641 reaction equation
[NH:1]1[C:9]2[C:5](=[CH:6][C:7]([P:18]([O:23][CH2:24][CH3:25])(=[O:22])[O:19][CH2:20][CH3:21])([P:10]([O:15][CH2:16][CH3:17])(=[O:14])[O:11][CH2:12][CH3:13])[CH:8]=2)[CH:4]=[CH:3][CH2:2]1.C([N-]C(C)C)(C)C.[Li+].[C:34]([S:37][CH2:38][CH2:39]I)(=[O:36])[CH3:35]>C1COCC1>[C:34]([S:37][CH2:38][CH2:39][C:8]1[C:7]([P:18]([O:23][CH2:24][CH3:25])(=[O:22])[O:19][CH2:20][CH3:21])([P:10]([O:11][CH2:12][CH3:13])(=[O:14])[O:15][CH2:16][CH3:17])[CH:6]=[C:5]2[C:9]=1[NH:1][CH2:2][CH:3]=[CH:4]2)(=[O:36])[CH3:35]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 190830772-Acetylthio-1-iodoethaneHCID 86752757Dihydro-1-pyrindine-6,6-diphosphonic acid tetraethyl ester

Product 1

HCID 86752760Dihydro-7-(2-acetylthioethyl)-1-pyrindine-6,6-bisphosphonic acid, tetraethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of dihydro-1-pyrindine-6,6-bisphosphonic acid, tetraethyl ester (7.0 mmol) [prepared as described in Example A, Part I] in anhydrous THF (100 ml) at -78° C. under argon is added dropwise a pregenerated solution of lithium diisopropyl amide (7.0 mmol) in THF (10 ml). After stirring 30 minutes, to this is added 2-acetylthio-1-iodoethane (7.5 mmol) in THF (25 ml). The reaction mixture is stirred at -78° C. for 5 hours then allowed to warm to room temperature and stirred overnight. The reaction is quenched by the addition of saturated aqueous ammonium chloride and then extracted with diethyl ether. The organic layers are combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The desired product is purified by flash chromatography using a 5-10% isopropanol in methylene chloride gradient on silica gel.

Workup

  1. stirringThe reaction mixture is stirred at -78° C. for 5 hours
  2. stirringstirred overnight
  3. customThe reaction is quenched by the addition of saturated aqueous ammonium chloride
  4. extractionextracted with diethyl ether
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe desired product is purified by flash chromatography

Sources & evidence

ORD record
ord-623e28d9728c475baea254e8982d4a02
Source dataset
uspto-grants-1998_06
Patent number
US05763611

Reaction notes

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