Methyl 4-bromo-3-(tetrahydropyran-2-yloxy)benzoate → Benzenemethanol, 4-bromo-3-[(tetrahydro-2H-pyran-2-yl)oxy]-

HRID 1685658

Reaction equation

HRID 1685658 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[Br:7][C:8]1[CH:17]=[CH:16][C:11]([C:12](OC)=[O:13])=[CH:10][C:9]=1[O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1>CCOCC>[Br:7][C:8]1[CH:17]=[CH:16][C:11]([CH2:12][OH:13])=[CH:10][C:9]=1[O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1

Participants

4

Reactant 2

HCID 16747841Methyl 4-bromo-3-(tetrahydropyran-2-yloxy)benzoateHCID 21226445Aluminium lithium hydride

Product 1

HCID 16749225Benzenemethanol, 4-bromo-3-[(tetrahydro-2H-pyran-2-yl)oxy]-Yield 88.1%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a suspension of LiAlH4 (0.72 g, 19.04 mmol) in anhydrous Et2O (90 mL) was slowly added a solution of methyl 4-bromo-3-(tetrahydropyran-2-yloxy)benzoate (4.0 g, 12.69 mmol) in anhydrous Et2O (10 mL). The mixture was stirred at room temperature for 2 h and then cautiously quenched with Na2SO4.10H2O (until gas evolution ceases). The solids were filtered off and washed with Et2O (100 mL). The combined organic fractions were then dried (Na2SO4) and concentrated in vacuo. The pale yellow residue was purified by flash column chromatography [SiO2, Et2O/n-hexane (7:3)] to give 4-bromo-3-(tetrahydropyran-2-yloxy)benzyl alcohol as a colourless oil (3.21 g, 88%). δH (270 MHz, CDCl3) 1.54-1.76 (m, 3H), 1.82-2.12 (m, 3H), 3.54-3.64 (m, 1H), 3.8-3.94 (m, 1H), 4.61 (d, J=4.9, 2H), 5.52 (m, 1H), 6.85 (dd, J=7.9, 1.5, 1H), 7.13 (d, J=2.0, 1H), 7.49 (d, J=7.9, 1H), Nb. ArCH2OH too broad to be observed; LC-MS (APCI+): tR=3.84 min, m/z 306.11 (C12H1581BrO4+H3O+), 304.13 (C12H1579BrO4+H3O+); HPLC: tR=2.34 min (96%); HRMS (FAB+) Found 289.02646; C12H16O381Br requires 289.02624.

Workup

  1. customcautiously quenched with Na2SO4.10H2O (until gas evolution ceases)
  2. filtrationThe solids were filtered off
  3. washwashed with Et2O (100 mL)
  4. dry with materialThe combined organic fractions were then dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe pale yellow residue was purified by flash column chromatography [SiO2, Et2O/n-hexane (7:3)]

Sources & evidence

ORD record
ord-788ddbbf617f487fae736d0e3d0493b3
Source dataset
uspto-grants-2012_04
Patent number
US08148415B2

Linked notes

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