Hydrochloric Acid → HCID 178525575, compound

HRID 70850Notes

Reaction equation

HRID 70850 reaction equation
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

Participants

7

Reactant 4

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

Product 1

HCID 178525575HCID 178525575, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

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) 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).

Workup

  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

Sources & evidence

ORD record
ord-90a791560fb64dd3b70fcb8ca0532265
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

Loading…