Phosphate → 114787-83-6

HRID 1609476Notes

Reaction equation

HRID 1609476 reaction equation
FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[CH3:16][C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][C:24]=1[N+:25]([O-:27])=[O:26])[CH2:20]O.C(N(CC)C(C)C)(C)C.[CH3:37][O:38][C:39](=[O:62])[C@H:40]([CH2:49][C:50]1[N:54]=[CH:53][N:52](C(OC(C)(C)C)=O)[CH:51]=1)[NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43].P([O-])([O-])([O-])=O>C(Cl)Cl>[CH3:37][O:38][C:39](=[O:62])[C@H:40]([CH2:49][C:50]1[N:54]([CH2:20][C:19]2[CH:22]=[CH:23][C:24]([N+:25]([O-:27])=[O:26])=[C:17]([CH3:16])[CH:18]=2)[CH:53]=[N:52][CH:51]=1)[NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:46])[CH3:47])=[O:43]

Participants

7

Reactant 5

HCID 1061PhosphateHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 5913603-Methyl-4-nitrobenzyl alcoholHCID 10904703N(alpha), N-(im)-Di-Boc-L-histidine methyl ester

Product 1

HCID 14457529114787-83-6Yield 106.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-70 °C

Procedure

Trifluoromethanesulfonic anhydride (10.00 g, 0.0354 mol) and dry methylene chloride (60 ml) were placed into a 500 ml separable flask having its interior atmosphere replaced with well dried nitrogen gas, and cooled to -70° C. Then a solution of 3-methyl-4-nitrobenzyl alcohol (5.34 g, 0.0325 mol) and N,N-diisopropylethylamine (6.2 ml, 0.0356 mol) in dry methylene chloride (40 ml) was added dropwise over a period of 15 minutes, followed by stirring for 30 minutes, after which a solution of N,1-bis-t-butoxycarbonyl-L-histidine methyl ester (XI-2) (10.00 g, 0.0271 mol) in dry methylene chloride (40 ml) was further added dropwise over a period of 20 minutes. Thereafter, the reaction flask was taken out of the cooling bath and the mixture was stirred at room temperature for 6 hours. The reaction mixture during rapid stirring was poured into a 0.2M phosphate buffer solution (about 400 ml) to separate the methylene chloride layer, and the residue was washed with a 0.2M phosphate buffer solution (about 400 ml), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain an orange-colored oily material (12.07 g). This crude oily material was purified by silica gel column chromatography (LiChroprep Si60, 300 g, chloroform/methanol=30/1) to obtain the objective compound (IX-2) (4.45 g; yield: 39.3%) as a light-yellow oily material.

Workup

  1. stirringthe mixture was stirred at room temperature for 6 hours
  2. stirringThe reaction mixture during rapid stirring
  3. customto separate the methylene chloride layer
  4. washthe residue was washed with a 0.2M phosphate buffer solution (about 400 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1742d3419bbf4ad68a50e88403d997dd
Source dataset
uspto-grants-1995_03
Patent number
US05401736

Reaction notes

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