Pyridine → Tetramethyl 1-(4-bromoacetamidobenzyl)methylenebisphosphonate

HRID 1841905Notes

Reaction equation

HRID 1841905 reaction equation
[NH2:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][CH:7]([P:14](=[O:19])([O:17][CH3:18])[O:15][CH3:16])[P:8](=[O:13])([O:11][CH3:12])[O:9][CH3:10])=[CH:4][CH:3]=1.N1C=CC=CC=1.[Br:28][CH2:29][C:30](Br)=[O:31]>C(Cl)Cl>[Br:28][CH2:29][C:30]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH:7]([P:14](=[O:19])([O:17][CH3:18])[O:15][CH3:16])[P:8](=[O:13])([O:11][CH3:12])[O:9][CH3:10])=[CH:20][CH:21]=1)=[O:31]

Participants

5

Reactant 3

HCID 1049PyridineHCID 61147Bromoacetyl bromideHCID 86624881Tetramethyl 1-(4-aminobenzyl)methylenebisphosphonate

Product 1

HCID 86624880Tetramethyl 1-(4-bromoacetamidobenzyl)methylenebisphosphonateYield 68.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 13 (0.959 g, 2.87 mmol) and pyridine (349 μL, 4.31 mmol) in CH2Cl2 was cooled in an ice-bath while stirring. A solution of bromoacetylbromide (250 μL, 2.87 mmol) in CH2Cl2 (5 mL) was added drop-wise and the resulting mixture was stirred for 4 h at that temperature. The reaction was quenched by the addition of water and the product was extracted with CH2Cl2. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude yellow solid was purified by silica gel chromatography resulting in 14 as a colorless solid (0.897 g, 67%). 1H NMR (400 MHz, CDCl3) δ 2.65 (tt, J=6.2, 24.4, 1H), 3.22 (dt, J=6.2, 17.4, 2H), 3.72 (d, J=3.7, 6H), 3.75 (d, J=3.7, 6H), 4.01 (s, 2H), 7.26 (d, J=8.6, 2H), 7.47 (d, J=8.6, 2H), 8.15 (bs, 1H): 31P (162 MHz, CDCl3) δ 26.33 (s, 2P).

Workup

  1. stirringthe resulting mixture was stirred for 4 h at that temperature
  2. customThe reaction was quenched by the addition of water
  3. extractionthe product was extracted with CH2Cl2
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude yellow solid was purified by silica gel chromatography

Sources & evidence

ORD record
ord-6ec2908508634960b60af6d331fee211
Source dataset
uspto-grants-2015_02
Patent number
US08946144B2

Reaction notes

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