Tetrabutylammonium Fluoride → (S)-1-[(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid methyl ester

HRID 2285349Notes

Reaction equation

HRID 2285349 reaction equation
ClC(Cl)(Cl)[CH2:3][O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:31])[C@@H:14]([NH:16][C:17](=[O:30])[C@@H:18]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:19]([CH3:21])[CH3:20])[CH3:15])[NH:8]1)=[O:6].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.CO>[CH3:3][O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:31])[C@@H:14]([NH:16][C:17](=[O:30])[C@@H:18]([NH:22][C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH:19]([CH3:21])[CH3:20])[CH3:15])[NH:8]1)=[O:6]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86706028(S)-1-[(S)-2-((S)-2-tert-butoxycarbonylamino-3-methylbutyrylamino)-propionyl]-hexahydropyridazine-3-carboxylic acid 2,2,2-trichloroethyl ester

Product 1

HCID 86706031(S)-1-[(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid methyl esterYield 91.2%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of (S)-1-[(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (3.01 g, 5.66 mmol) in tetrahydrofuran/methanol (1:1, 60 mL) was stirred at 0° C. Tetra-n-butylammonium fluoride (1 M in tetrahydrofuran, 11.3 mL, 11.3 mmol) was added and the reaction mixture was stirred at room temperature for 22 h. The solvent was removed in vacuo and the residue was purified by silica gel chromatography using a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 1:1 afford the title compound (2.14 g, 91%) as a white foam. 1H NMR (300 MHz, CDCl3) δ □0.91 (d, J=6.9 Hz, 3H), 0.95 (d, J=6.9 Hz, 3H), 1.32 (d, J=6.9 Hz, 3H), 1.46 (s, 9H), 1.61-2.17 (m, 6H), 2.80-2.88 (m, 1H), 3.47-3.58 (m, 1H), 3.73-3.78 (s, 3H), 3.94-4.02 (m, 1H), 4.33-4.38 (m, 1H), 5.13 (d, J=8.3 Hz, 1H), 5.27-5.37 (m, 1H), 6.75 (d, J=7.6 Hz, 1H). LCMS (m/z) 415.1 [M+H], Tr=3.17 min.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-ed39ccff8d1446dea8392768f44dfb00
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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