Lipoic acid → 3-[(3R)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]propyl 5-[(3R)-1,2-dithiolan-3-yl]pentanoate

HRID 1747016Notes

Reaction equation

[S:1]1[CH2:5][CH2:4][C@@H:3]([CH2:6][CH2:7][CH2:8][CH2:9][C:10]([OH:12])=[O:11])[S:2]1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][C@H:27]([OH:29])[C@@H:26]([OH:30])[C@H:25]([OH:31])[C@H:24]1[CH2:32][OH:33]>CN(C=O)C>[S:1]1[CH2:5][CH2:4][C@@H:3]([CH2:6][CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:20][CH2:21][CH2:22][N:23]2[CH2:28][CH:27]([OH:29])[CH:26]([OH:30])[C@H:25]([OH:31])[CH:24]2[CH2:32][OH:33])=[O:11])[S:2]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of 5-[(3R)-1,2-dithiolan-3-yl]pentanoic acid 6 (500 mg, 2.42 mmol) in DMF (5 mL) was added K2CO3 (1.4 g, 9.69 mmol) at room temperature and the mixture was stirred for 30 min. Then a solution of hydrochloride salt of (2R,3R,4R,5S)-1-(3-chloropropyl)-2-(hydroxymethyl)piperidine-3,4,5-triol 5 (581 mg, 2.1 mmol) in DMF (5 mL) was added to the reaction mixture and the mixture was heated at 60° C. for 16 h. The reaction mixture was then filtered through a celite pad, washed with DCM (100 mL). The filtrate was concentrate under reduced pressure to get crude which was purified by column chromatography using 100-200 mesh silica gel and eluting with 6% methanol in DCM to afford 3-[(3R)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]propyl 5-[(3R)-1,2-dithiolan-3-yl]pentanoate, compound 7 (300 mg, 30%) as brown oil.

Workup

filtrationThe reaction mixture was then filtered through a celite pad
washwashed with DCM (100 mL)
concentrationThe filtrate was concentrate under reduced pressure
customto get crude which
customwas purified by column chromatography
washeluting with 6% methanol in DCM

Sources & evidence

ORD record: ord-3656cae150704ddbbea5fd2cae918dff
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09150557B1

Reaction notes

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