1,4-Dioxane → HCID 59607555, compound

HRID 70826Notes

Reaction equation

HRID 70826 reaction equation
[CH2:1]([O:3][C:4](=[O:35])[CH2:5][C@H:6]([NH:23][C:24](=[O:34])[CH2:25][CH2:26][C:27]([O:29]C(C)(C)C)=[O:28])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[O:21][CH3:22])=[CH:10][CH:9]=1)[CH3:2].O1CCOCC1>Cl>[CH2:1]([O:3][C:4](=[O:35])[CH2:5][C@H:6]([NH:23][C:24](=[O:34])[CH2:25][CH2:26][C:27]([OH:29])=[O:28])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[O:21][CH3:22])=[CH:10][CH:9]=1)[CH3:2]

Participants

4

Reactant 2

HCID 312751,4-DioxaneHCID 67208801(R)-tert-butyl 4-(4-ethoxy-1-(5'-fluoro-2'-methoxybiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobutanoate

Product 1

HCID 59607555HCID 59607555, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution of (R)-tert-butyl 4-(4-ethoxy-1-(5′-fluoro-2′-methoxybiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobutanoate, (65 mg, 0.13 mmol) in 4M HCl in 1,4-dioxane (671 μL, 2.68 mmol) is stirred at room temperature. After stirring for 1 hour, the reaction mixture is concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN), and then lyophilized to give (R)-4-(4-ethoxy-1-(5′-fluoro-2′-methoxybiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobutanoic acid (23 mg). HPLC retention time=1.66 minutes (condition D); MS (m+1)=432.3; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.17 (t, J=7.1 Hz, 3 H) 2.21-2.32 (m, 2 H) 2.32-2.40 (m, 2 H) 2.40-2.48 (m, 2 H) 2.77 (d, J=6.8 Hz, 2 H) 3.74 (s, 3 H) 4.03 (q, J=7.1 Hz, 2 H) 4.19-4.33 (m, 1 H) 7.04-7.20 (m, 3 H) 7.23 (d, J=8.1 Hz, 2 H) 7.43 (d, J=8.1 Hz, 2 H) 7.93 (d, J=8.3 Hz, 1 H)

Workup

  1. concentrationthe reaction mixture is concentrated under reduced pressure
  2. customThe obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)

Sources & evidence

ORD record
ord-fdc5fdd8027d4584a0290592676b5d2b
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

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