Cyclopentanol → (4-Cyclopentyloxy-3-methoxy-phenyl)-acetic acid methyl ester

HRID 1063816Notes

Reaction equation

HRID 1063816 reaction equation
[CH:1]1([OH:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:26][O:27][C:28](=[O:39])[CH2:29][C:30]1[CH:35]=[CH:34][C:33](O)=[C:32]([O:37][CH3:38])[CH:31]=1.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[CH3:26][O:27][C:28](=[O:39])[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[C:32]([O:37][CH3:38])[CH:31]=1

Participants

6

Reactant 4

HCID 7298CyclopentanolHCID 11776TriphenylphosphineHCID 85214Methyl 4-hydroxy-3-methoxyphenylacetateHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 23402498(4-Cyclopentyloxy-3-methoxy-phenyl)-acetic acid methyl esterYield 66.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Cyclopentanol (7.7 ml, 85 mmol) and triphenylphosphine (28 g, 107 mmol) were added to a solution of (4-hydroxy-3-methyoxy-phenyl)-acetic acid methyl ester (14 g, 71 mmol) in tetrahydrofuran (280 ml) under nitrogen at 0° C. Diethylazodicarboxylate (15.7 ml, 100 mmol) was then added dropwise and the reaction was allowed to warm to room temperature and stirred for 44 hours. The solvent was removed under reduced pressure, pentane (200 ml) was added and the suspension was filtered. The filtrate was concentrated under reduced pressure and purified by flash column chromatography on silica gel eluting with a solvent gradient of cyclohexane:ethyl acetate (90:10 changing to 85:15, by volume) to give (4-cyclopentyloxy-3-methoxy-phenyl)-acetic acid methyl ester (12.4 g) as a colourless oil. 1H NMR (400 MHz, CD3OD): δ=6.79-6.85 (2H, m), 6.73-6.79 (1H, d), 4.73-4.79 (1H, brs), 3.79 (3H, s), 3.64 (3H, s), 3.53 (2H, s), 1.74-1.89 (6H, m), 1.56-1.67 (2H, m) ppm. LRMS (electrospray): m/z [M+Na]+ 287. Anal. Found C, 68.01; H, 7.74. C15H20O4 requires C, 68.16; H, 7.63%.

Workup

  1. customThe solvent was removed under reduced pressure, pentane (200 ml)
  2. additionwas added
  3. filtrationthe suspension was filtered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. custompurified by flash column chromatography on silica gel eluting with a solvent gradient of cyclohexane:ethyl acetate (90:10 changing to 85:15, by volume)

Sources & evidence

ORD record
ord-163dcd96946e4e8a99647e5b9adeb967
Source dataset
uspto-grants-2005_11
Patent number
US06967204B2

Reaction notes

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