1-Hydroxybenzotriazole → HCID 21341439, compound

HRID 2185431Notes

Reaction equation

HRID 2185431 reaction equation
F[C:2](F)(F)C(O)=O.C(O[C:13]([N:15]1[CH2:22][C@@H:21]([OH:23])[CH2:20][C@H:16]1[C:17]([OH:19])=[O:18])=[O:14])(C)(C)C.[C:24]([O:28][C:29]([N:31]([CH2:33]C(O)=O)[CH3:32])=[O:30])([CH3:27])([CH3:26])[CH3:25].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.C(N(CC)CC)C>[CH3:2][O:19][C:17](=[O:18])[C@@H:16]1[CH2:20][C@H:21]([OH:23])[CH2:22][N:15]1[C:13](=[O:14])[CH2:32][N:31]([C:29]([O:28][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:30])[CH3:33]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 83692Glycine, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86758123HCID 86758123, compound

Product 1

HCID 21341439HCID 21341439, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

Trifluoroacetic acid (10 mL) was added to a solution of N-tert-butoxycarbonyl-cis-4-hydroxy-L-proline methyl ester (Compound D101 (J), 1.10 g) in dichloromethane (10 mL) at 0° C. After stirring at 0° C. for 10 min and at room temperature for 3 hr, the mixture was evaporated in vacuo to give a crude N-tert-butoxycarbonyl-cis-4-hydroxy-L-proline trifluoroacetate. The crude N-tert-butoxycarbonyl-cis-4-hydroxy-L-proline trifluoroacetate was dissolved in dichloromethane (20 mL), and N-tert-butoxycarbonyl-sarcosine (844 mg), triethylamine (1.25 mL), 1-hydroxybenzotriazole (663 mg), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (856 mg) were added at 0° C. After stirring at 0° C. for 30 min and at room temperature for 17 hr, the solvent was removed in vacuo. The residue was diluted with 1 N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated sodium hydrogen carbonate, water, and brine, dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue as purified by silica gel column chromatography (chloroform then chloroform-methanol=50:1 to 30:1, v/v) to afford the title compound (452 mg) as a colorless oil. The compound appears as a mixture of rotamers: 1H NMR (400 MHz, CDCl3) δ 1.42 and 1.46 (each s, total 9H), 2.04-2.14 (m, 1H), 2.26-2.39 (m, 1H), 2.94 (s, 3H), 3.52-4.17 (m, 4H), 3.75 and 3.77 (each s, total 3H), 4.17-4.28 (m, 1H), and 4.38-4.62 (m, 2H).

Workup

  1. customthe solvent was removed in vacuo
  2. additionThe residue was diluted with 1 N hydrochloric acid
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated sodium hydrogen carbonate, water, and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated in vacuo
  7. customThe residue as purified by silica gel column chromatography (chloroform

Sources & evidence

ORD record
ord-0882c9da82b646e0a594c2457deb6475
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

Loading…