Hydrochloric Acid → HCID 59607891, compound

HRID 70860Notes

Reaction equation

HRID 70860 reaction equation
[C:1]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:17]C(OC(C)(C)C)=O)[CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[CH:3][CH:2]=1.Cl.O1CCOCC1.[C:38]1(=[O:44])[O:43][C:41](=[O:42])[CH2:40][CH2:39]1.CCN(C(C)C)C(C)C>ClCCl>[C:1]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:17][C:38](=[O:44])[CH2:39][CH2:40][C:41]([OH:43])=[O:42])[CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[CH:3][CH:2]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7922Succinic anhydrideHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 59607924HCID 59607924, compound

Product 1

HCID 59607891HCID 59607891, compoundYield 36.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (R)-tert-butyl 4-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)butanoate (26.4 mg, 0.064 mmol) is added 4M HCl in 1,4-dioxane (0.321 ml, 1.283 mmol) at room temperature. The reaction mixture is stirred for 45 minutes and concentrated under reduced pressure. To a solution of the obtained residue in dichloromethane (0.4 mL) is added succinic anhydride (7.70 mg, 0.077 mmol) and DIPEA (0.013 mL, 0.077 mmol). The reaction mixture is allowed to stir at room temperature for 14 hours and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C-18, H2O (0.1% TFA)/CH3CN) to give (R)-4-(1-(biphenyl-4-yl)-4-tert-butoxy-4-oxobutan-2-ylamino)-4-oxobutanoic acid (9.5 mg). HPLC retention time=1.70 minutes (condition A); MS (ES+)=412.1 (m+1); 356.0 (m-tBu+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.48 (s, 9 H) 2.36-2.51 (m, 4 H) 2.64-2.67 (m, 2 H) 2.87 (A of ABX, Jab=13.5 Hz, Jax=5.7 Hz, 1 H), 2.97 (Jab=13.5 Hz, Jbx=6.2 Hz, 1 H) 7.24-7.26 (m, 2 H) 7.31-7.35 (m, 1 H) 7.43 (t, J=7.75 Hz, 2 H) 7.53(d, J=8.0 Hz, 2 H) 7.57 (d, J=7.6 HZ, 2 H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. stirringto stir at room temperature for 14 hours
  3. concentrationconcentrated under reduced pressure
  4. customThe obtained residue is purified by RP-HPLC (SunFire C-18, H2O (0.1% TFA)/CH3CN)

Sources & evidence

ORD record
ord-4c106406360042adb711970b50202b2c
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

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