3,4-dihydro-2H-pyran → 2-(6-Bromo-2-methyl-2-phenylhexyloxy)-tetrahydropyran

HRID 873301Notes

Reaction equation

HRID 873301 reaction equation
[O:1]1[CH:6]=[CH:5][CH2:4][CH2:3][CH2:2]1.[Br:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([CH3:21])([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:13][OH:14]>C(Cl)Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([CH3:21])([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[CH2:13][O:14][CH:6]1[CH2:5][CH2:4][CH2:3][CH2:2][O:1]1

Participants

5

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 113002282-Methyl-2-phenyl-6-bromohexanol

Product 1

HCID 112104532-(6-Bromo-2-methyl-2-phenylhexyloxy)-tetrahydropyranYield 70.4%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 6344DichloromethaneSolvent

Procedure

Under N2 atmosphere and cooling with an ice bath, 3,4-dihydro-2H-pyran (33.86 g, 0.40 mol) was added dropwise to a stirred solution of 206d (88.0 g, 0.32 mol) and p-toluenesulfonic acid hydrate (0.05 g, 0.03 mmol) in CH2Cl2 (700 mL). After the addition, the reaction mixture was allowed to warm to room temperature and stirred overnight. The solution was filtered through aluminum oxide (160 g) and the aluminum oxide was washed with CH2Cl2 (800 mL). The filtrate was concentrated in vacuo and purified by flash chromatography on silica gel (hexanes/ethyl acetate=10/1) to give 207d (80.0 g, 70%) as an oil. 1H NMR (CDCl3): δ 7.40-7.14 (m 10H), 4.53 (t, 1H, J=3.4), 4.49 (t, 1H, J=3.4), 3.82 (d, 1H, J=9.4), 3.81 (t, 1H, J=9.4), 3.76-3.60 (m, 2H), 3.44 (m, 2H), 3.36 (d, 2H, J=9.4), 3.33 (t, 4H, J=7.0), 1.90-1.42 (m, 14H), 1.79 (t, 4H, J=6.8), 1.37 (s, 6H), 1.34-1.10 (m, 6H). 13C NMR (CDCl3=77.0 ppm): δ 145.67, 127.91, 127.91, 126.39, 126.37, 125.7, 98.95, 98.81, 76.11, 76.07, 62.78, 61.77, 61.66, 41.88, 41.78, 37.93, 37.75, 33.50, 33.44, 30.59, 30.44, 25.41, 25.37, 22.77, 22.71, 22.62, 19.65, 19.23, 19.15. HRMS (LSIMS, nba): Calcd for C15H28BrO2 (MH+): 355.1272, found: 355.1272.

Workup

  1. temperatureUnder N2 atmosphere and cooling with an ice bath
  2. additionAfter the addition
  3. filtrationThe solution was filtered through aluminum oxide (160 g)
  4. washthe aluminum oxide was washed with CH2Cl2 (800 mL)
  5. concentrationThe filtrate was concentrated in vacuo
  6. custompurified by flash chromatography on silica gel (hexanes/ethyl acetate=10/1)

Sources & evidence

ORD record
ord-1817afbaa8bf4919b89a0a9859e955d6
Source dataset
uspto-grants-2015_03
Patent number
US08975300B2

Reaction notes

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