Methyl 4-iodobenzoate → Methyl 4-(2-cyclopropyl-1-hydroxyethyl)benzoate

HRID 537432Notes

Reaction equation

I[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.[Cl-].[Li+].[CH:19]1([CH2:22][CH:23]=[O:24])[CH2:21][CH2:20]1>O1CCCC1>[CH:19]1([CH2:22][CH:23]([C:2]2[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=2)[OH:24])[CH2:21][CH2:20]1

Participants

Conditions

Temperature: -40 °C

Procedure

To a −40° C. solution of methyl 4-iodobenzoate (0.39 g, 1.5 mmol) in tetrahydrofuran (7.5 mL) was added isopropylmagnesium chloride-lithium chloride (1.5 mL, 1.3 M in THF, 1.95 mmol) dropwise. After stirring for 30 minutes at −40° C., 2-cyclopropylacetaldehyde (190 mg, 2.26 mmol) was added dropwise. The resulting mixture was then stirred at room temperature for 1 hour. The reaction mixture was quenched with saturated ammonium chloride and partitioned between water and ethyl acetate. The layers were separated and the aqueous was extracted again with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. Purification by column chromatography gave (+/−)-methyl 4-(2-cyclopropyl-1-hydroxyethyl)benzoate (150 mg, 45%). 1HNMR (400 MHz, CDCl3, δ): 7.89 (d, 2H), 7.32 (d, 2H), 4.75-4.72 (m, 1H), 3.79 (s, 3H), 1.60-1.51 (m, 2H), 0.60-0.51 (m, 1H), 0.49-025 (m, 2H), 0.07-0.12 (m, 2H).

Workup

stirringThe resulting mixture was then stirred at room temperature for 1 hour
customThe reaction mixture was quenched with saturated ammonium chloride
custompartitioned between water and ethyl acetate
customThe layers were separated
extractionthe aqueous was extracted again with ethyl acetate
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customPurification by column chromatography

Sources & evidence

ORD record: ord-61b1434b877a4fc9987f05235c9155e2
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08859591B2

Reaction notes

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