2-Phenylvinylboronic acid → Enalapril acid

HRID 1977494Notes

Reaction equation

HRID 1977494 reaction equation
[NH2:1][C@H:2]([C:4]([OH:6])=O)[CH3:3].[NH:7]1[CH2:14][CH2:13][CH2:12][C@H:8]1[C:9]([OH:11])=[O:10].O.[C:16]([OH:20])(=[O:19])[CH:17]=O.[C:21]1([CH:27]=[CH:28]B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O.CO.[Pd]>[CH3:3][C@H:2]([NH:1][C@H:17]([C:16]([OH:20])=[O:19])[CH2:28][CH2:27][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:4]([N:7]1[C@H:8]([C:9]([OH:11])=[O:10])[CH2:12][CH2:13][CH2:14]1)=[O:6]

Participants

7

Reactant 3

HCID 27343812-Phenylvinylboronic acidHCID 15620607Glyoxylic acid, monohydrateHCID 22825802HCID 22825802, compound

Product 1

HCID 5462501Enalapril acidYield 80%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Alanine-proline (1,000 mg, 5.37 mmol), glyoxylic acid monohydrate (544 mg, 5.91 mml) and 2-phenylethenyl boronic acid (1,192 mg, 8 mmol) were vigorously stirred together in water (7 mL) for 48 hours. The precipitate was filtered, washed with acetone (2×10 mL) and dried to give a single crystalline product (1,488 mg, 80% yield, >99% de) the structure of which was confirmed with X-ray crystallography. 1H NMR (360 MHz, DCl/D2O) δ 7.10-7.25 (br, 5H), 6.92 (d, J=15.6 Hz, 1H), 5.78 (dd, J=15.6 Hz, 9.8 Hz, 1H), 4.75 (d, J=9.8 Hz, 1H), 4.15 (q, J=6.8 Hz, 1H), 3.84 (m, 1H), 3.20 (m, 2H), 1.58 (m, 2H), 1.41 (d, J=6.8 Hz, 3H), 1.01-1.35 (m, 2H). 13C NMR (90 MHz, DCl/D2O) δ 174.2, 168.7, 168.2, 142.6, 133.4, 130.4, 129.3, 127.1, 114.7, 62.3, 59.4, 54.0, 47.4, 28.0, 24.0, 15.1. HRMS-CI calcd for C18H22N2O5 (M+H+) 347.1528, found 347.1598. Anal. Calcd for C18H22N2O5: C, 62.42; H, 6.40; N, 8.09. Found: C, 62.46; H, 6.41 N, 8.02. This compound was hydrogenated in methanol with Pd/C as catalyst to give pure enalaprilat.

Workup

  1. filtrationThe precipitate was filtered
  2. washwashed with acetone (2×10 mL)
  3. customdried
  4. customto give a single crystalline product (1,488 mg, 80% yield, >99% de) the structure of which

Sources & evidence

ORD record
ord-6d706c1099374b4d8a39f00fe67c8a4a
Source dataset
uspto-grants-2001_05
Patent number
US06232467B1

Reaction notes

Loading…