Hydrochloric Acid → HCID 57506778, compound

HRID 1266718Notes

Reaction equation

Cl.C([O:4][C:5](=[O:33])[CH:6]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:30](=[NH:32])[NH2:31])=[CH:26][CH:25]=1)[C:7]1[CH:12]=[C:11]([O:13][CH2:14][CH3:15])[CH:10]=[C:9]([O:16][C@@H:17]2[CH2:21][CH2:20][O:19][CH2:18]2)[C:8]=1[F:22])C.[Li+].[OH-].Cl>C1COCC1>[C:30]([C:27]1[CH:28]=[CH:29][C:24]([NH:23][CH:6]([C:7]2[CH:12]=[C:11]([O:13][CH2:14][CH3:15])[CH:10]=[C:9]([O:16][C@@H:17]3[CH2:21][CH2:20][O:19][CH2:18]3)[C:8]=2[F:22])[C:5]([OH:33])=[O:4])=[CH:25][CH:26]=1)(=[NH:31])[NH2:32]

Participants

Conditions

Temperature: 0 °C

Procedure

A suspension of 170 mg (RS)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-[(R)-tetrahydro-furan-3-yloxy]-phenyl]-acetic acid ethyl ester hydrochloride described in example 3.8 in 5 ml THF was cooled to 0° C. and treated with 1.8 ml 1N LiOH solution. The mixture was stirred for 2 hrs at 0° C., then neutralized with 1N HCl. The precipitate was filtered off and washed with H2O and Et2O to yield 129 mg of (RS)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-[(R)-tetrahydro-furan-3-yloxy]-phenyl]-acetic acid as an off-white solid. This isomeric mixture was separated into the diastereomers by preparative HPLC on a chiral stationary phase (Chiralpak AD) using heptane/isopropanol/trifluoroacetic acid (75:25:0.2) as a mobile phase to give, after neutralization, (R)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-[(R)-tetrahydro-furan-3-yloxy]-phenyl]-acetic acid and (S)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-(R)-tetrahydro-furan-3-yloxy]-phenyl]-acetic acid as off-white solids.

Workup

filtrationThe precipitate was filtered off
washwashed with H2O and Et2O

Sources & evidence

ORD record: ord-b5bfd44e0cbe4b77b0de9cbebc732fe5
Source dataset: uspto-grants-2003_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06548694B2

Reaction notes

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