Diisopropylethylamine → [(3,5-Bis-benzyloxy-pyridine-2-carbonyl)-amino]-acetic acid tert-butyl ester

HRID 2188531Notes

Reaction equation

HRID 2188531 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.Cl.[C:27]([O:31][C:32](=[O:35])[CH2:33][NH2:34])([CH3:30])([CH3:29])[CH3:28].C(N(C(C)C)CC)(C)C>CN(C=O)C.ON1C2C=CC=CC=2N=N1>[C:27]([O:31][C:32](=[O:35])[CH2:33][NH:34][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:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:12][N:11]=1)=[O:24])([CH3:30])([CH3:29])[CH3:28]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2725036Glycine tert-butyl ester hydrochlorideHCID 534879953,5-Bis(benzyloxy)picolinic acid

Product 1

HCID 59513083[(3,5-Bis-benzyloxy-pyridine-2-carbonyl)-amino]-acetic acid tert-butyl esterYield 99%

Reagents, catalysts & solvents 2

HCID 757711-HydroxybenzotriazoleCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3,5-bis-benzyloxy-pyridine-2-carboxylic acid, 2, (2.36 g, 6.36 mmol) in DMF (20 mL) at room temperature under N2 is added 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide (EDCI) (1.83 g, 9.54 mmol) and 1-hydroxybenzotriazole (HOBt) (0.086 g, 0.64 mmol). The mixture is stirred for 15 minutes after which time glycine tert-butyl ester hydrochloride (1.60 g, 9.54 mmol) and diisopropylethylamine (DIPEA) (3.32 ml, 19.08 mmol) are added. The resulting solution is stirred at room temperature for 48 hours then concentrated under reduced pressure. The resulting brown oil is purified over silica (EtOAc) to afford 3.04 g (99% yield) of the desired compound as a yellow solid. 1H NMR (250 MHz, CDCl3) δ ppm 8.19 (1H, t, J=5.2 Hz), 8.01-8.08 (2H, m), 7.27-7.54 (9H, m), 6.97 (1H, d, J=2.4 Hz), 5.24 (2H, s), 5.13 (2H, s), 4.17 (2H, d, J=5.2 Hz), 1.51 (9H, s). HPLC-MS: m/z 449 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-c5272d4dbc2d467a9fc3f423df702425
Source dataset
uspto-grants-2012_12
Patent number
US08323671B2

Reaction notes

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