Succinic anhydride → HCID 49822297, compound

HRID 1945000Notes

Reaction equation

HRID 1945000 reaction equation
Cl.[NH2:2][C@H:3]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=2[F:24])=[CH:13][CH:12]=1)[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[C:25]1(=[O:31])[O:30][C:28](=[O:29])[CH2:27][CH2:26]1.CCN(C(C)C)C(C)C>ClCCl>[Cl:23][C:21]1[CH:20]=[CH:19][C:18]([F:24])=[C:17]([C:14]2[CH:15]=[CH:16][C:11]([CH2:10][C@@H:3]([NH:2][C:25](=[O:31])[CH2:26][CH2:27][C:28]([OH:30])=[O:29])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:12][CH:13]=2)[CH:22]=1

Participants

5

Reactant 3

HCID 7922Succinic anhydrideHCID 81531DiisopropylethylamineHCID 86648192HCID 86648192, compound

Product 1

HCID 49822297HCID 49822297, compoundYield 86.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-ethyl 3-amino-4-(5′-chloro-2′-fluorobiphenyl-4-yl)butanoate hydrochloride (293 mg, 0.777 mmol), succinic anhydride (93 mg, 0.932 mmol) and DIPEA (0.204 mL, 1.165 mmol) in dichloromethane (4 mL) is allowed to stir for 1.5 hours. The reaction is quenched with 1 M aqueous HCl and extracted with dichloromethane. The organic layer is separated and concentrated under reduced pressure. The resulting residue is purified by preparative HPLC using a gradient of 20% MeCN/water (0.1% TFA) to 100% MeCN to give (R)-4-(1-(5′-chloro-2′-fluorobiphenyl-4-yl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoic acid (294 mg). HPLC retention time=1.03 minutes (condition B); MS (m+1)=436.2; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.28 (t, J=7.07 Hz, 3H) 2.46-2.58 (m, 4H) 2.64-2.68 (m, 2H) 2.87 (A of ABX, Jab=13.64 Hz, Jax=7.83 Hz, 1H) 2.99 (B of ABX, Jab=13.64 Hz, Jbx=6.57 Hz, 1H) 4.11-4.22 (m, 2H) 4.47-4.56 (m, 1H) 6.60 (br d, J=8.59 Hz, 1H) 7.05-7.10 (m, 1H) 7.23-7.27 (m, 3H) 7.39-7.41 (m, 1H) 7.44-7.46 (m, 2H).

Workup

  1. customThe reaction is quenched with 1 M aqueous HCl
  2. extractionextracted with dichloromethane
  3. customThe organic layer is separated
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-16a91024256e423bb88972ca299d37c7
Source dataset
uspto-grants-2013_03
Patent number
US08394853B2

Reaction notes

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