Phenol → HCID 68792636, compound

HRID 1713582Notes

Reaction equation

HRID 1713582 reaction equation
[CH2:1]([C:3]1[CH:16]=[CH:15][C:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[CH:5][CH:4]=1)[CH3:2].[H-].[Na+].CC1C=CC(S(O[CH2:30][CH2:31][C@@:32]2([O:71][CH3:72])[C@H:37]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C@@H:36]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C@H:35]([O:54][CH2:55][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)[C@@H:34]([CH2:62][O:63][CH2:64][C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)[O:33]2)(=O)=O)=CC=1.[O-]C1C=CC=CC=1.C1(O)C=CC=CC=1>CN(C=O)C.CCOC(C)=O>[CH2:39]([O:38][C@@H:37]1[C@@H:36]([O:46][CH2:47][C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C@H:35]([O:54][CH2:55][C:56]2[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=2)[C@@H:34]([CH2:62][O:63][CH2:64][C:65]2[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=2)[O:33][C@:32]1([CH2:31][CH2:30][O:14][C:11]1[CH:12]=[CH:13][C:8]([CH2:7][C:6]2[CH:15]=[CH:16][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=2)=[CH:9][CH:10]=1)[O:71][CH3:72])[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

8

Reactant 5

HCID 996Phenol2×HCID 24758Sodium hydrideHCID 119047PhenolateHCID 67182117HCID 67182117, compoundHCID 86621844HCID 86621844, compound

Product 1

HCID 68792636HCID 68792636, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

4-(4-Ethylbenzyl)phenol (3) (28 mg, 0.13 mmol) was dissolved in DMF (200 μL). NaH (5 mg, 60%/mineral oil, 0.13 mmol) was added. After 5 min, a solution of 2-((2S,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-2-methoxytetrahydro-2H-pyran-2-yl)ethyl 4-methylbenzenesulfonate (9) (50 mg in 200 μL DMF) was added to the phenoxide solution. After 2 h, the reaction was heated to 60° C. for 2 h, then stirred overnight at room temperature (15h). The reaction mixture was diluted with EtOAc and washed with NaHCO3 (2×). The aqueous layers were combined and back-extracted with EtOAc (2×). The organic layers were combined, dried, and concentrated provide 72 mg. 1HNMR indicated that the product was present, but with extraneous phenol contamination. The sample was purified by preparative thin-layer chromatography (SiO2, eluting with 40% EtOAc/hexanes) to provide a film (26.1 mg, approx 50%) that still had contaminating phenol present. The material was carried forward to the next step. 1H NMR (300 MHz, CDCl3) δ ppm: 6.99-7.32 (m, 25H), 6.69 (m, 3H), 4.48-4.97 (m, 8H), 4.13 (t, J=9 Hz, 1H), 3.94 (m, 1H), 3.86 (s, 2H), 3.55-3.80 (m, 6H), 3.26 (s, 3H), 2.60 (q, J=15.3, 7.8 Hz, 2H), 2.27 (m, 2H), 1.21 (t, J=8.1 Hz). LC/MS tR=6.47 min, calcd for C52H56O7: 792.4, found 815.4 (M+Na)+.

Workup

  1. waitAfter 2 h
  2. washwashed with NaHCO3 (2×)
  3. extractionback-extracted with EtOAc (2×)
  4. customdried
  5. concentrationconcentrated
  6. customprovide 72 mg
  7. customThe sample was purified by preparative thin-layer chromatography (SiO2, eluting with 40% EtOAc/hexanes)
  8. customto provide a film (26.1 mg, approx 50%) that

Sources & evidence

ORD record
ord-078b823d5c5e46b78d13c54a13a17f33
Source dataset
uspto-grants-2010_09
Patent number
US07795228B2

Reaction notes

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