4-Bromophenol → HCID 178419399, compound

HRID 84229Notes

Reaction equation

HRID 84229 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[O:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[O:15][C@@H:16]1[CH2:21][CH2:20][C@H:19]([CH2:22]O)[CH2:18][CH2:17]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:22][C@@H:19]2[CH2:18][CH2:17][C@H:16]([O:15][CH:10]3[CH2:11][CH2:12][CH2:13][CH2:14][O:9]3)[CH2:21][CH2:20]2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 78084-BromophenolHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 178520984HCID 178520984, compound

Product 1

HCID 178419399HCID 178419399, compoundYield 48.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-Bromophenol (0.344 g, 2.0 mmol) was added to a solution of (+/−)-[cis-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methanol (0.387 g, 1.81 mmol) in THF (10 mL). Triphenylphosphine (0.474 g, 1.81 mmol) and triethylamine (0.183 g, 1.81 mmol) were added. The resulting solution was cooled to 0° C. and DIAD (0.365 g, 1.81 mmol) was added by dropwise addition. After 18 hours the reaction was quenched by addition of water and extracted with ether (2×100 mL). The organic layers were combined and washed with 1N NaOH (2×100 mL) then water (2×100 mL). The organic layer was dried (MgSO4), filtered and concentrated to give a clear oil. Purification by flash column chromatography on a Biotage SNAP cartridge Kp-sil 100g column (hexanes/ethyl acetate 9:1) afforded the title compound as a white solid (324 mg, 48%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.41-1.75 (m, 11 H) 1.75-1.98 (m, 4 H) 3.39-3.54 (m, 1 H) 3.70-3.80 (m, 2 H) 3.83-3.97 (m, 2 H) 4.55-4.69 (m, 1 H) 6.66-6.82 (m, 2H) 7.29-7.42 (m, 2 H).

Workup

  1. customAfter 18 hours the reaction was quenched by addition of water
  2. extractionextracted with ether (2×100 mL)
  3. washwashed with 1N NaOH (2×100 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a clear oil
  8. customPurification by flash column chromatography on a Biotage SNAP cartridge Kp-sil 100g column (hexanes/ethyl acetate 9:1)

Sources & evidence

ORD record
ord-f438f017ef3d4e7a8afb1bb3031f2281
Source dataset
uspto-grants-2014_09
Patent number
US08846933B2

Reaction notes

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