Dimethyl methylphosphonate → [6-(2,3-Dihydro-1H-pyrrolo [2,3-b]pyridin-6-yl)-2-oxo-hexyl]-phosphonic acid dimethyl ester

HRID 860087Notes

Reaction equation

HRID 860087 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].[Li]CCCC.C([O:17][C:18](=O)[CH2:19][CH2:20][CH2:21][CH2:22][C:23]1[N:28]=[C:27]2[NH:29][CH2:30][CH2:31][C:26]2=[CH:25][CH:24]=1)CCC>C1COCC1>[CH3:4][O:3][P:2]([CH2:1][C:18](=[O:17])[CH2:19][CH2:20][CH2:21][CH2:22][C:23]1[N:28]=[C:27]2[NH:29][CH2:30][CH2:31][C:26]2=[CH:25][CH:24]=1)(=[O:7])[O:5][CH3:6]

Participants

5

Reactant 3

HCID 12958Dimethyl methylphosphonateHCID 696666885-(2,3-Dihydro-1H-pyrrolo[2,3-b]pyridin-6-yl)-pentanoic acid butyl esterHCID 178418339Butyllithium

Product 1

HCID 20622453[6-(2,3-Dihydro-1H-pyrrolo [2,3-b]pyridin-6-yl)-2-oxo-hexyl]-phosphonic acid dimethyl esterYield 89.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of dimethyl methylphosphonate (1.35 g, 10.9 mmol) in anhydrous THF (20 mL) was cooled to −78° and treated dropwise with 2.6 M n-BuLi (4.1 mL). After stirring at −78° for 15 min, a solution of ester 23-6 (0.750 g, 2.71 mmol) in THF (10 mL) was added dropwise and the resulting solution stirred for 15 min at −78°, quenched with sat. NH4Cl (25 mL), then extracted with CHCl3 (1×25 mL), and the organic layer was applied to PCTLC (4 mm, 10% MeOH/CHCl3) affording 0.79 g (89% yield) of 23-7.

Workup

  1. stirringthe resulting solution stirred for 15 min at −78°
  2. customquenched with sat. NH4Cl (25 mL)
  3. extractionextracted with CHCl3 (1×25 mL)

Sources & evidence

ORD record
ord-c8a87f9c586f4109b2d0e251681ec63a
Source dataset
uspto-grants-2006_12
Patent number
US07153862B2

Reaction notes

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