Lithium Hydroxide → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(tetrahydropyran-2-carbonyl)amino]pentanoic Acid

HRID 508400

反応式

C([O:3][C:4](=[O:24])[C@H:5]([OH:23])[CH2:6][C@H:7]([NH2:22])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)=[CH:11][CH:10]=1)C.[O:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]1[C:31](O)=[O:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Li+].[OH-]>CN(C=O)C>[Cl:21][C:17]1[CH:16]=[C:15]([C:12]2[CH:13]=[CH:14][C:9]([CH2:8][C@@H:7]([NH:22][C:31]([CH:26]3[CH2:27][CH2:28][CH2:29][CH2:30][O:25]3)=[O:32])[CH2:6][C@@H:5]([OH:23])[C:4]([OH:3])=[O:24])=[CH:10][CH:11]=2)[CH:20]=[CH:19][CH:18]=1

参加物

実験手順

(2R,4R)-4-Amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester (50 mg, 144 μmol) was added to a solution of tetrahydro-pyran-2-carboxylic acid (1.2 eq., 165 μmol) and HATU (71.1 mg, 187 μmol) in DMF (250 μL), followed by the addition of DIPEA (75 μL, 431 μmol). The resulting mixture was stirred at room temperature for 1 hour. 10 M aqueous LiOH (115 μL, 1.2 mmol) was added and the mixture was stirred for an additional 1 hour. The mixture was washed with DCM (1 mL) and the aqueous layer was acidified with concentrated HCl (250 μL) and extracted with DCM (2×1 mL). The DCM extracts were combined and concentrated in vacuo, and the resulting crude liquid was purified by reverse phase preparative HPLC to yield the title compound (32.6 mg). MS m/z [M+H]+ calc'd for C23H26ClNO5, 432.15. found 432.2.

後処理

stirringthe mixture was stirred for an additional 1 hour
washThe mixture was washed with DCM (1 mL)
extractionextracted with DCM (2×1 mL)
concentrationconcentrated in vacuo
customthe resulting crude liquid was purified by reverse phase preparative HPLC

出典と根拠

ORDレコード: ord-66aa00106297452ca21f25fe31250cac
出典データセット: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US09096496B2

反応式

参加物

反応物 5

生成物 1

試薬・触媒・溶媒 1

実験手順

後処理

出典と根拠

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