Sulfuric Acid → (S)-2-methyl-5-phenylpentanoic acid

HRID 709104Notes

Reaction equation

OC[C@H](N[C:11](=[O:23])[C@@H:12]([CH3:22])[CH2:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)C1C=CC=CC=1.S(=O)(=O)(O)[OH:25]>O1CCOCC1>[CH3:22][C@@H:12]([CH2:13][CH2:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:11]([OH:23])=[O:25]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution consisting of (S)—N—((R)-2-hydroxy-1-phenylethyl)-2-methyl-5-phenylpentanamide (19mb(i), 3.5 g, 11.24 mmol) in 1,4-dioxane (80 mL) was added aqueous sulfuric acid (36 mL, 3 N solution) and the mixture was stirred overnight at 80° C. The reaction mixture was extracted with ethyl acetate three times and the organic layers were combined, dried over sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography. Elution with ethyl acetate-heptane-acetic acid (30:70:0.4 v/v/v) afforded the title compound (2.4 g, quantitative yield) as a clear oil; Rf 0.48 (solvent system: 30:70:0.4 v/v/v ethyl acetate-heptane-acetic acid; HPLC retention time 26.0 minutes; Chiralpak IA, 5μ, 4.6×25 mm, ultraviolet detector at 208 nm 0.75 ml/min 99:1:0.5 v/v heptanes-2-propanol-acetic acid; MS (ESI−) m/z 191.1 (M−H)−; 1H-NMR (CDCl3) δ 7.33-7.27 (m, 2H), 7.22-7.16 (m, 3H), 2.67-2.60 (m, 2H), 2.56-2.46 (m, 1H), 1.80-1.60 (m, 3H), 1.59-1.36 (m, 1H), 1.25-1.14 (m, 3H); [α]Tλ=α/cl, [α]21.9D=+0.089/(0.01501 g/1.5 mL)(0.5)=+17.79° (c=1, CHCl3).

Workup

extractionThe reaction mixture was extracted with ethyl acetate three times
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated under vacuum
customThe residue was purified by silica gel chromatography
washElution with ethyl acetate-heptane-acetic acid (30:70:0.4 v/v/v)

Sources & evidence

ORD record: ord-d6ae09e8b4054e12ae4ddb3ecd080979
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09180116B2

Reaction notes

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