Hydrochloric Acid → HCID 57920162, compound

HRID 19197Notes

Reaction equation

HRID 19197 reaction equation
Cl.C(OC([N:9]1[C@H:13]([CH2:14][N:15]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:41])[C@@H:22]([N:27]3[CH2:31][C:30]([O:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[Cl:39])=[CH:29][C:28]3=[O:40])[CH2:23][CH:24]([CH3:26])[CH3:25])=[N:16]2)[CH2:12][O:11]C1(C)C)=O)(C)(C)C>C(OCC)C>[NH2:9][C@@H:13]([CH2:12][OH:11])[CH2:14][N:15]1[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:41])[C@@H:22]([N:27]2[CH2:31][C:30]([O:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[Cl:39])=[CH:29][C:28]2=[O:40])[CH2:23][CH:24]([CH3:26])[CH3:25])=[N:16]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66894751HCID 66894751, compound

Product 1

HCID 57920162HCID 57920162, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Hydrochloric acid gas was bubbled into a stirred solution of (R)-4-(3-{(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidin-3-carboxylic acid t-butyl ester (1.00 g, 16.63 mmol) in diethyl ether (20 mL) for 30 seconds. The reaction mixture was then stirred at room temperature for 30 min during which a white solid precipitates out of solution. The diethyl ether was decanted off and the solid washed with three portions of diethyl ether. The crude product was purified via supercritical fluid chromatography on a DAICEL AD column, 25% methanol, 70 mL/min to afford (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2-amino-3-hydroxy-propyl)-1H-pyrazol-3-yl]-amide (362 mg, 47%) as a white solid: LR-ES-MS m/z calculated for C22H28ClN5O4 [M]+ 461, observed 462 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 1.34-1.85 (m, 5H), 3.00 (br. s., 1H), 3.22 (br. s., 2H), 3.80 (dd, J=13.4, 6.9 Hz, 1H), 4.02 (dd, J=13.4, 5.0 Hz, 1H), 4.21 (d, J=18.4 Hz, 1H), 4.61 (d, J=18.4 Hz, 1H), 4.65-4.75 (m, 1H), 4.79 (s, 1H), 4.89 (dd, J=9.8, 4.1 Hz, 1H) H), 6.42 (s, 1H), 7.31-7.42 (m, 1H), 7.42-7.55 (m, 2H), 7.57 (br. s., 1H), 7.65 (d, J=7.2 Hz, 1H), 10.79 (br. s., 1H).

Workup

  1. customprecipitates out of solution
  2. customThe diethyl ether was decanted off
  3. washthe solid washed with three portions of diethyl ether
  4. customThe crude product was purified via supercritical fluid chromatography on a DAICEL AD column, 25% methanol, 70 mL/min

Sources & evidence

ORD record
ord-dd64afcd71e34aca8834f1c1e14b9f82
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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