Diethyl Ether → HCID 25138431, compound

HRID 1044445Notes

Reaction equation

HRID 1044445 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:37]O)=[C:13]([CH:36]=1)[O:14][CH2:15][C:16]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][O:26][CH3:27])=[CH:20][C:19]=1[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOCC.C[O-].[Na+]>C(#N)C.C(Cl)Cl>[CH2:29]([O:28][C:19]1[CH:20]=[C:21]([O:24][CH2:25][O:26][CH3:27])[CH:22]=[CH:23][C:18]=1[C:16]1[CH2:15][O:14][C:13]2[C:12]([CH:37]=1)=[CH:11][CH:10]=[C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH:36]=2)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 80811Triphenylphosphonium bromideHCID 10942334Sodium MethoxideHCID 44603676HCID 44603676, compound

Product 1

HCID 25138431HCID 25138431, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(5-Benzyloxy-2-hydroxymethyl-phenoxy)-1-(2-benzyloxy-4-methoxymethyloxy-phenyl)-ethanone (0.514 g, 1 mmol) in 5 mL of acetonitrile was added triphenyl phosphine hydrobromide (0.343 g, 1 mmol) and the suspension stirred at RT for ca. 4 hours. After disappearance of starting material (TLC), organic solvent was evaporated at 20° C. to provide a yellowish solid. The solid was redissolved in 5 mL of DCM and anhydrous ether was added with constant stirring. The white Wittig's ylide precipitated. This product was used directly in the next step without further purification. The crude product (ca. 0.80 g) was dissolved in 10 mL of methanol followed by addition of sodium methoxide (0.108 g, 2 mmol). The suspension was refluxed for ca. 12 hours after which it was allowed to come to RT. A white solid precipitated. The precipitate was filtered and the filtrate was concentrated to ca. one-half the volume and again refluxed for 4 hours after which it provided additional product upon cooling to RT. The combined product was recrystallized from methanol (ca. 30 mL) to obtain 0.374 g (78%) of white solid: mp 132-134° C.; TLC Rf0.43, in hexanes:EtOAc (5:1); 1H NMR (600 MHz, acetone-d6) δ 7.51-7.31 (m, 10H, 2×C6H5), 7.28-7.27 (d, 1H, J=8.4 Hz, Ar—H5), 7.01-7.00 (d, 1H, J=7.8 Hz, Ar—H6′), 6.8 (d, 1H, J=2.4 Hz, Ar—H8), 6.69-6.67 (dd, 1H, 2J=8.4 Hz, 3J=2.4 Hz, Ar—H6), 6.60 (s, 1H, Ar—H4), 6.57-6.55 (dd, 1H, 2J=8.4 Hz, 3J=2.4 Hz, Ar—H5′), 6.46 (d, 1H, J=2.4 Hz, Ar—H3′), 5.2 (s, 2H, O—CH2—O), 5.13 (s, 2H, PhCH2), 5.09 (s, 2H, PhCH2), 4.92 (s, 2H, H2), 3.42 (s, 3H, OCH3); 13C NMR (100 MHz, acetone-d6) δ 161.1, 159.9, 158.9, 156.3, 138.9, 138.5, 130.6, 130.5, 130, 129.9, 129.4, 129.3, 129.2, 129, 128.9, 123.2, 122.6, 118.8, 109.6, 103.6, 103.2, 95.8, 71.8, 71.1, 69.6, 56.7; analysis calcd. for C31H28O5. C, 77.01; H, 5.80. found: C, 77.0; H, 5.80.

Workup

  1. customAfter disappearance of starting material (TLC), organic solvent was evaporated at 20° C.
  2. customto provide a yellowish solid
  3. customThe white Wittig's ylide precipitated
  4. customThis product was used directly in the next step without further purification
  5. dissolutionThe crude product (ca. 0.80 g) was dissolved in 10 mL of methanol
  6. temperatureThe suspension was refluxed for ca. 12 hours after which it
  7. customto come to RT
  8. customA white solid precipitated
  9. filtrationThe precipitate was filtered
  10. concentrationthe filtrate was concentrated
  11. temperatureagain refluxed for 4 hours after which it
  12. customprovided additional product
  13. temperatureupon cooling to RT
  14. customThe combined product was recrystallized from methanol (ca. 30 mL)

Sources & evidence

ORD record
ord-84ad5fc3681a4830867501c6bf0e7155
Source dataset
uspto-grants-2013_10
Patent number
US08563599B2

Reaction notes

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