Hydrochloric Acid → HCID 178525575、化合物

HRID 881826ノート

反応式

HRID 881826 の反応式
C([O:3][C:4](=[O:35])[CH2:5][C@H:6]([NH:20][C:21]([C:23]1[N:27](CC2C=CC=CC=2)[N:26]=[N:25][N:24]=1)=[O:22])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)C.C(OC(=O)C[C@H](NC(C1N=NN(CC2C=CC=CC=2)N=1)=O)CC1C=CC(C2C=CC=CC=2)=CC=1)C.[Li+].[OH-].Cl>CCO.C1COCC1>[C:11]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:10]=[CH:9][C:8]([CH2:7][C@@H:6]([NH:20][C:21]([C:23]2[NH:27][N:26]=[N:25][N:24]=2)=[O:22])[CH2:5][C:4]([OH:35])=[O:3])=[CH:13][CH:12]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 59607597HCID 59607597、化合物HCID 67208758(R)-3-[(2-benzyl-2H-tetrazole-5-carbonyl)-amino]-4-biphenyl-4-yl-butyric acid ethyl ester

生成物 1

HCID 178525575HCID 178525575、化合物

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a mixture of (R)-3-[(1-benzyl-1H-tetrazole-5-carbonyl)-amino]-4-biphenyl-4-yl-butyric acid ethyl ester and (R)-3-[(2-benzyl-2H-tetrazole-5-carbonyl)-amino]-4-biphenyl-4-yl-butyric acid ethyl ester (180 mg, 0.383 mmol) in EtOH (1 mL) and THF (1 mL) is added aqueous 1M LiOH (2 mL). After stirring for 0.5 hour, the reaction mixture is acidified with aqueous 1M HCl. The mixture is extracted with ethyl acetate, dried over Na2SO4, and concentrated under reduced pressure. The residue is dissolved in MeOH and hydrogenated with 10% Pd/C at room temperature for 3 hours and at 40° C. for 2 hours. The reaction mixture is concentrated and purified by reverse phase HPLC to give (R)-4-biphenyl-4-yl-3-[(1H-tetrazole-5-carbonyl)-amino]-butyric acid. HPLC retention time=1.18 minutes (condition D); MS (m+1)=352; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.56 (dd, J=5.81, 15.92 Hz, 1H), 2.67 (dd, J=7.58, 15.92 Hz, 1H), 2.85-2.99 (m, 2H), 4.55-4.64 (m, 1H), 7.26-7.35 (m, 3H), 7.43 (dd, J=7.83, 7.83 Hz, 2H), 7.56 (d, J=8.08 Hz, 2H), 7.62 (d, J=7.07 Hz, 2H), 9.28 (d, 8.84 Hz, 1H), 12.28 (s, 1H).

後処理

  1. extractionThe mixture is extracted with ethyl acetate
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue is dissolved in MeOH and hydrogenated with 10% Pd/C at room temperature for 3 hours and at 40° C. for 2 hours
  5. concentrationThe reaction mixture is concentrated
  6. custompurified by reverse phase HPLC

出典と根拠

ORDレコード
ord-dc3ac79602494cd4b9ae00d7cfb32ad9
出典データセット
uspto-grants-2015_03
特許番号
US08993631B2

反応ノート

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