Boron trifluoride → HCID 12241075, compound

HRID 2220821Notes

Reaction equation

HRID 2220821 reaction equation
B(F)(F)F.[OH:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:22])[C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:12][O:13]2)=[CH:8][CH:7]=1.C(C(C1C=[CH:36][C:35]([OH:38])=CC=1O)=O)C1C=CC=CC=1.C1([C:46](CC2C=CC=CC=2)=[O:47])C=CC=CC=1>>[OH:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](=[O:22])[C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:12]([C:46]([O:38][CH2:35][CH3:36])=[O:47])[O:13]2)=[CH:8][CH:7]=1

Participants

5

Reactant 4

HCID 6356Boron trifluorideHCID 99482-PhenylacetophenoneHCID 138005Benzyl 2,4-dihydroxyphenyl ketoneHCID 53768917-Hydroxyisoflavone

Product 1

HCID 12241075HCID 12241075, compound

Procedure

Deoxybenzoins undergo α-keto formylation, intramolecular acetal formation, and a facile dehydration to give the pyrone ring C and hence, the isoflavones as shown in Scheme 1, Step 2 and below. Substituted deoxybenzoins were synthesized by reacting appropriate substituted phenyl acetic acids with properly substituted resorcinols in the presence of BF3. The starting material (7-hydroxy isoflavone, compound 1) for the synthesis of the 7-O-substituted isoflavones was prepared by cyclization of 2,4-dihydroxyphenyl benzyl ketone (Aldrich Chemical Co. Milwaukee, Wis.) as described by WO 91/15483, and shown in steps 2 and 3 of scheme 1, and further described in Gao et al. (2003) Bioorganic & Medicinal Chemistry, in press. 7-Hydroxy-2-ethoxycarbonylisoflavone (compound 20) was prepared by cyclization of the corresponding deoxybenzoin in the presence of an appropriate formyl equivalent as shown in Li, D. Y.; Gao, Z. J.; Ji, Q. E. Synthesis of isoflavones derivatives (I)-7-methoxy-3′-N, N-dialkylaminomethyl-4′-hydroxy isoflavones (Chinese J. Med. Chem. 1991, 1 (2), 38-42). The 2-carboxy derivatives (compounds 16, 21, and 22) were obtained by hydrolyzing their respective ethyl esters. The 4′-amino derivatives (compounds 32 and 33) were prepared by reducing their corresponding 4′-nitro derivatives (compounds 27 and 28) under the condition set forth in WO 91/15483, and Li, D. Y.; Gao, Z. J.; Ji, Q. E. Synthesis of isoflavones derivatives (I)-7-methoxy-3′-N, N-dialkylaminomethyl-4′-hydroxy isoflavones. Chinese J. Med. Chem. 1991, 1 (2), 38-42. Full explanations of the syntheses are set forth below. All compounds synthesized were purified by Sephadex-LH-20 and/or silica gel columns. Products were identified by 1HNMR, 13C-NMR, MS, and elemental analyses. Purity of all compounds prepared in this study was greater than 97.8% as judged by HPLC with UV detection at 254 mn. Molecular weights, melting points, molecular formulae, and elemental analysis data of these analogs are included in EXAMPLE IV, below.

Workup

  1. customwere obtained
  2. customwere prepared
  3. customAll compounds synthesized
  4. customwere purified by Sephadex-
  5. customPurity of all compounds prepared in this study

Sources & evidence

ORD record
ord-3dd0e832b9f9472c9f1004651b0a5648
Source dataset
uspto-grants-2008_05
Patent number
US07368434B2

Reaction notes

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