Hydrochloric Acid → Bempedoic acid

HRID 1466706Notes

Reaction equation

HRID 1466706 reaction equation
[BH4-].[Na+].[O:3]=[C:4]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([CH3:26])([CH3:25])[C:22]([OH:24])=[O:23])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([CH3:15])([CH3:14])[C:11]([OH:13])=[O:12].C(OCC)(=O)C.Cl>CO.O>[OH:3][CH:4]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([CH3:26])([CH3:25])[C:22]([OH:24])=[O:23])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([CH3:15])([CH3:14])[C:11]([OH:13])=[O:12]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 4311764Sodium borohydride2×HCID 113368222,2,14,14-Tetramethyl-8-oxopentadecanedioic acid

Product 1

HCID 10472693Bempedoic acidYield 60%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

Under nitrogen atmosphere, sodium borohydride (0.06 g, 1.6 mmol) was added to a stirred solution of 8-oxo-2,2,14,14-tetramethylpentadecanedioic acid (1.18 g, 3.4 mmol) in methanol (50 mL) at 0° C. The reaction progress was monitored by thin layer chromatography (silica; hexanes:ethyl acetate=50:50). Additional sodium borohydride was added after 1 h (0.48 g, 13 mmol). After 8 h, the reaction mixture was hydrolyzed with water (50 mL) and acidified with concentrated hydrochloric acid (3 mL) to pH 1. The solution was diluted with water (50 mL) and extracted with dichloromethane (4×25 mL). The combined organic layers were washed with saturated sodium chloride solution (2×30 mL), dried over magnesium sulfate, concentrated in vacuo, and dried in high vacuo to give 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid (0.7 g, 60%) as a very viscous oil. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm): 7.42 (br. s, 3H), 3.59 (br. s, 1H), 1.65-1.00 (m, 20H), 1.18 (s, 12H). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm): 184.5, 71.8, 42.1, 40.5, 37.0, 29.8, 25.2, 25.1, 24.9, 24.8. FIRMS (FAB): Calcd. for C19H37O5 (MH+): 345.2635. found: 345.2646. HPLC: 83.8% purity.

Workup

  1. extractionextracted with dichloromethane (4×25 mL)
  2. washThe combined organic layers were washed with saturated sodium chloride solution (2×30 mL)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customdried in high vacuo

Sources & evidence

ORD record
ord-109ac50a97c342af8d31e912b65d987b
Source dataset
uspto-grants-2015_04
Patent number
US09000041B2

Reaction notes

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