Triethylamine → di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-(3-tert-butoxy-4-{2-[(methylsulfonyl)oxy]ethoxy}benzyl)-L-glutamate

HRID 591329Notes

Reaction equation

HRID 591329 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:10][C@H:11]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][OH:29])=[C:22]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:21]=1)[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:49][S:50](Cl)(=[O:52])=[O:51]>ClCCl>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:10][C@H:11]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][O:29][S:50]([CH3:49])(=[O:52])=[O:51])=[C:22]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:21]=1)[C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 117812680di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-[3-tert-butoxy-4-(2-hydroxyethoxy)benzyl]-L-glutamate

Product 1

HCID 117812705di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-(3-tert-butoxy-4-{2-[(methylsulfonyl)oxy]ethoxy}benzyl)-L-glutamateYield 79.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 100 mg (0.172 mmol) di-tert-butyl (4S)—N-(tert-butoxycarbonyl)-4-[3-tert-butoxy-4-(2-hydroxyethoxy)benzyl]-L-glutamate, 25.6 mg (0.253 mmol) triethylamine in ca. 1 ml dichloromethane was added 25.5 mg (0.222 mmol) methane sulphonic acid chloride at 0° C. The reaction mixture was stirred at room temperature for 4 hours. Further 25.6 mg (0.253 mmol) triethylamine and 25.5 mg (0.222 mmol) methane sulphonic acid chloride were added. The reaction mixture is stirred for another 4 hours. The reaction mixture is diluted with dichloro methane. The organic phase washed with saturated aqueous ammonium chloride, saturated aqueous sodium hydrogen carbonate solution, dried with sodium sulfate and concentrated in vacuo. The crude product is purified by column chromatography (silica gel, hexane/ethylacetate gradient: 5:1→1:99). The desired product was obtained in 79.6% yield (99 mg, 0.14 mmol).

Workup

  1. stirringThe reaction mixture is stirred for another 4 hours
  2. washThe organic phase washed with saturated aqueous ammonium chloride, saturated aqueous sodium hydrogen carbonate solution
  3. dry with materialdried with sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product is purified by column chromatography (silica gel, hexane/ethylacetate gradient: 5:1→1:99)

Sources & evidence

ORD record
ord-cae0b229b1544d88a7019e08c3af45ee
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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