Triacetoxyperiodinane → methyl 4-(tetrahydro-2H-pyran-4-carbonyl)benzoate

HRID 1520867Notes

Reaction equation

HRID 1520867 reaction equation
[OH:1][CH:2]([CH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)[C:3]1[CH:13]=[CH:12][C:6]([C:7]([O:9][CH2:10]C)=[O:8])=[CH:5][CH:4]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[O:17]1[CH2:18][CH2:19][CH:14]([C:2]([C:3]2[CH:4]=[CH:5][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:12][CH:13]=2)=[O:1])[CH2:15][CH2:16]1

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 68156522ethyl 4-(hydroxy(tetrahydro-2H-pyran-4-yl)methyl)benzoate

Product 1

HCID 68156933methyl 4-(tetrahydro-2H-pyran-4-carbonyl)benzoateYield 16.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of methyl 4-iodobenzoate (1.21 mL, 7.24 mmol) in THF (12 ml) at −40° C. was added TurboGrignard (1.3 M in THF, 6.13 ml, 7.97 mmol) dropwise. The mixture was stirred for approximately 60 minutes whereupon, tetrahydro-2H-pyran-4-carbaldehyde (0.761 ml, 0.724 mmol) was added dropwise. The mixture was stirred for 15 minutes and slowly warmed to rt over 12 hours. The reaction was quenched with HCl (1 N, aq.) and the aq. layer was extracted with EtOAc (3×75 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to provide ethyl 4-(hydroxy(tetrahydro-2H-pyran-4-yl)methyl)benzoate. Crude mixture used into the next step without any further purification. Step B: A round bottom flask was charged with ethyl 4-(hydroxy(tetrahydro-2H-pyran-4-yl)methyl)benzoate (1.9 g, 7.2 mmol), the Dess-Martin reagent (3.66 g, 8.63 mmol) and DCM (15 mL). The reaction was stirred at room temperature overnight. Reaction diluted with DCM and solid filtered off. The mother liquor concentrated and loaded onto a silica gel column. Purification by silica gel flash chromatography (ethyl acetate/DCM) provide methyl 4-(tetrahydro-2H-pyran-4-carbonyl)benzoate (290 mg, mmol) as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.75-1.96 (m, 4H) 3.45-3.62 (m, 3H) 3.97 (s, 3H) 4.07 (dt, J=11.88, 3.25 Hz, 2H) 7.98-8.02 (m, 2H) 8.12-8.17 (m, 2H); MS (M−1): 246.8.

Workup

  1. customCrude mixture used into the next step without any further purification
  2. customReaction
  3. filtrationfiltered off
  4. concentrationThe mother liquor concentrated
  5. customPurification by silica gel flash chromatography (ethyl acetate/DCM)

Sources & evidence

ORD record
ord-426cd850c2b74a06979fdea3eb4272fa
Source dataset
uspto-grants-2015_07
Patent number
US09073871B2

Reaction notes

Loading…