Ethyl Acetate → (2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid

HRID 1469601Notes

Reaction equation

HRID 1469601 reaction equation
C([O:3][C:4](=[O:31])[C@H:5]([CH3:30])[CH2:6][C@H:7]([NH:21][C:22](=[O:29])[CH2:23][C:24]1[S:25][CH:26]=[CH:27][CH:28]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)C.[OH-].[Na+].C(OCC)(=O)C>C(O)C>[C:12]1([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:11]=[CH:10][C:9]([CH2:8][C@@H:7]([NH:21][C:22](=[O:29])[CH2:23][C:24]2[S:25][CH:26]=[CH:27][CH:28]=2)[CH2:6][C@@H:5]([CH3:30])[C:4]([OH:31])=[O:3])=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 67506137(2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid ethyl ester

Product 1

HCID 59608316(2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Next, to a solution of (2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid ethyl ester (0.287 mmol) in ethanol (10 mL) is added aqueous 1M NaOH (2 mL, 6.97 mmol) and the mixture is stirred at room temperature for 18 hours. The mixture is poured into ethyl acetate and is washed with aqueous 1M HCl, the organic phase is dried over magnesium sulfate and the solvent is removed under reduced pressure. The residue is purified by preparative HPLC using a gradient of MeCN/water (0.1% TFA). The proper fractions are lyophilized to furnish (2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid. HPLC Retention time 1.23 minutes (condition A); MS 408.3 (M+1); 1H NMR (400 MHz, MeOD-d4) δ ppm 1.16 (d, J=7.07 Hz, 3H), 1.50 (m, 1H), 1.96 (m, 1H), 2.52 (m, 1H), 2.72 (dd, J=7.71 Hz, 7.58 Hz, 1H), 2.84 (dd, J=5.81 Hz, 5.66 Hz, 1H), 3.64 (d, J=1.26 Hz, 2H), 4.20 (m, 1H), 6.82 (m, 1H), 6.89 (m, 1H), 7.21 (m, 3H), 7.32 (m, 1H), 7.42 (m, 2H), 7.46 (m, 2H), 7.57 (m, 2H), 7.95 (d, J=8.59 Hz, 1H).

Workup

  1. washis washed with aqueous 1M HCl
  2. dry with materialthe organic phase is dried over magnesium sulfate
  3. customthe solvent is removed under reduced pressure
  4. customThe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-c28bb814090148118b2711cedb892000
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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