Benzyltrimethylammonium methoxide → HCID 23388389, compound

HRID 990389Notes

Reaction equation

HRID 990389 reaction equation
[CH:1]([NH:5][C@@H:6]([CH:10]([CH3:12])[CH3:11])[C:7]([OH:9])=O)([CH2:3][CH3:4])[CH3:2].[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[CH2:21][CH2:22][CH2:23][NH2:24])=[CH:16][CH:15]=1.C(N(CC)C(C)C)(C)C.C[O-].C([N+](C)(C)C)C1C=CC=CC=1>CN(C=O)C.C(OCC)C>[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[CH2:21][CH2:22][CH2:23][NH:24][C:7](=[O:9])[C@@H:6]([NH:5][CH:1]([CH2:3][CH3:4])[CH3:2])[CH:10]([CH3:12])[CH3:11])=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 8504Benzyltrimethylammonium methoxideHCID 81531DiisopropylethylamineHCID 12837668HCID 12837668, compoundHCID 13530069HCID 13530069, compound

Product 1

HCID 23388389HCID 23388389, compoundYield 38.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 291 mg (1.68 mmol) (S)-2-sec-butylamino-3-methyl-butyric acid, 500 mg (1.68 mmol) 4,4-bis-(4-fluoro-phenyl)-butylamine, 0.29 mL (1.68 mmol) N,N-diisopropylethylamine, and 1.5 mL (3.36 mmol) benzyltrimethylammonium methoxide (40% solution in methanol) in 4 mL dry DMF was cooled to 3° C. and 637 mg (1.68 mmol) O-Benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)uronium hexafluorophosphate was added and the resulting mixture stirred at 3° for 30 minutes, warmed to 25° C., and stirred an additional 30 minutes at which time it was diluted with 20 mL diethyl ether, and washed with 20 mL saturated aqueous sodiumbicarbonate solution and twice with 20 mL brine, dried over anhydrous sodium sulfate and concentrated at reduced pressure. The residue thus obtained was further purified by silica gel chromatography using 70% ethyl acetate/hexanes as eluant, followed by conversion to the hydrochloride salt by treating with excess diethyl ether which had been saturated with hydrogen chloride gas to give 270 mg (35%) of titled compound: mp 77-81° C. APCI-MS m/z417.4 (MH+).

Workup

  1. stirringstirred an additional 30 minutes at which time it
  2. washwashed with 20 mL saturated aqueous sodiumbicarbonate solution and twice with 20 mL brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated at reduced pressure
  5. customThe residue thus obtained
  6. customwas further purified by silica gel chromatography
  7. additionby treating with excess diethyl ether which

Sources & evidence

ORD record
ord-b8559fb2cad546128d29a7cf232f46e3
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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