Tetrahydrofuran → (4-Anilino-3-benzoyl-4-oxobutylidene)bisphosphonic acid tetraethyl ester

HRID 1450212Notes

Reaction equation

HRID 1450212 reaction equation
S(N1[CH2:20][C:19](=[O:21])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)C1)(C1C=CC(C)=CC=1)(=O)=O.[CH2:22]([O:24][P:25]([C:30]([P:32](=[O:39])([O:36][CH2:37][CH3:38])[O:33][CH2:34][CH3:35])=[CH2:31])(=[O:29])[O:26][CH2:27][CH3:28])[CH3:23].[CH2:40]1[CH2:50][CH2:49][N:48]2[C:43](=NCC[CH2:47]2)[CH2:42][CH2:41]1.C1C[O:54]CC1>C(OCC)(=O)C.CCOCC>[CH2:37]([O:36][P:32]([CH:30]([P:25](=[O:29])([O:26][CH2:27][CH3:28])[O:24][CH2:22][CH3:23])[CH2:31][CH:20]([C:19](=[O:21])[C:18]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:47]([NH:48][C:43]1[CH:42]=[CH:41][CH:40]=[CH:50][CH:49]=1)=[O:54])(=[O:39])[O:33][CH2:34][CH3:35])[CH3:38]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 5896332-tosyl-2,3-dihydroisoquinolin-4(1H)-oneHCID 11022954Tetraethyl vinylidene phosphonate

Product 1

HCID 10370027(4-Anilino-3-benzoyl-4-oxobutylidene)bisphosphonic acid tetraethyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

The amide (II, 2.50 g), ethenylidenebisphosphonic acid tetraethyl ester (I, 3.00 g), and DBU (0.25 ml) are heated to 50° C. in THF (20 ml) for 30 min. The reaction is cooled, diluted with ethyl acetate, washed with hydrochloric acid (1 N), saturated sodium bicarbonate, and saline, then dried with magnesium sulfate, and concentrated under reduced pressure. The crude material is chromatographed eluting with ethyl acetate. The compound is left overnight on the bench whereupon a solid formed. This is slurried in ether, filtered and dried in under reduced pressure to give the title compound, mp 104°-105°; MS (m/e) 539, 447, 288, 239, 163, 120, 105 and 93; IR (mineral oil) 1699, 1682, 1606, 1599, 1589, 1549, 1442 and 1241 cm-1 ; NMR (CDCl3) 9.55, 8.08, 7.57, 7.46, 7.30, 7.09, 4.96, 4.17, 2.58, 1.38 and 1.28 δ; CMR (CDCl3) 212.4, 195.5, 167.1, 138.0, 136.2, 133.7, 128.9, 128.8, 128.5, 124.3, 119.6, 63.1 (m), 54.0, 34.5, 25.9 and 16.3 δ.

Workup

  1. temperatureThe reaction is cooled
  2. washwashed with hydrochloric acid (1 N), saturated sodium bicarbonate, and saline
  3. dry with materialdried with magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material is chromatographed
  6. washeluting with ethyl acetate
  7. customformed
  8. filtrationfiltered
  9. customdried in under reduced pressure

Sources & evidence

ORD record
ord-6642ae7b824c4c41b5683174dcc82d5a
Source dataset
uspto-grants-1997_02
Patent number
US05602115

Reaction notes

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