Aminoisobutyric acid → 2-[(3,5-Bis-benzyloxy-pyridine-2-carbonyl)-amino]-2-methylpropionic acid methyl ester

HRID 2188523Notes

Reaction equation

HRID 2188523 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:23](O)=[O:24])=[N:11][CH:12]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26]N(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:47][C:48]([CH3:53])([CH3:52])[C:49]([OH:51])=[O:50].C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH3:26][O:50][C:49](=[O:51])[C:48]([NH:47][C:23]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:14][C:13]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[CH:12][N:11]=1)=[O:24])([CH3:53])[CH3:52]

Participants

7

Reactant 5

HCID 6119Aminoisobutyric acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 534879953,5-Bis(benzyloxy)picolinic acid

Product 1

HCID 595130922-[(3,5-Bis-benzyloxy-pyridine-2-carbonyl)-amino]-2-methylpropionic acid methyl esterYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3,5-bis-benzyloxy-pyridine-2-carboxylic acid, 2, (1.0 g, 2.99 mmol) in DMF (20 mL) at room temperature under N2 is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) (0.925 g, 5.97 mmol) and 1-hydroxybenzotriazole (HOBt) (0.806 g, 5.97 mmol). The mixture is stirred for 15 minutes after which α-aminoisobutyric acid (0.917 g, 5.97 mmol) and diisopropylethyl-amine (DIPEA) (1.56 mL, 8.96 mmol) are added. The resulting solution is stirred at room temperature for 16 hours then concentrated under reduced pressure. The resulting brown oil is purified over silica (EtOAc:heptane 1:1) to afford 0.58 g (45% yield) of the desired compound as a colorless solid. 1H NMR (250 MHz, CDCl3) δ ppm 8.13 (1H, s), 8.02 (1H, d, J=2.3 Hz), 7.31-7.48 (10H, m), 6.90 (1H, d, J=2.3 Hz), 5.19 (2H, s), 5.10 (2H, s), 3.74 (3H, s), 1.58 (6H, s). HPLC-MS: m/z 435 [M+H]+.

Workup

  1. additionare added
  2. concentrationthen concentrated under reduced pressure
  3. customThe resulting brown oil is purified over silica (EtOAc:heptane 1:1)

Sources & evidence

ORD record
ord-1e67feeafa304c40875e83a793e392e8
Source dataset
uspto-grants-2012_12
Patent number
US08323671B2

Reaction notes

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