Triethylamine → Methyl 2-(3,5-bis((methylsulfonyloxy)methyl) phenyl)-5,8,11,14,17,20, 23,26,29,32, 35,38-dodecaoxa-2-azahentetracontan-41-oate

HRID 2403522Notes

Reaction equation

HRID 2403522 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([N:11]([CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][O:42][CH2:43][CH2:44][O:45][CH2:46][CH2:47][O:48][CH2:49][CH2:50][C:51]([O:53][CH3:54])=[O:52])[CH3:12])[CH:6]=[C:7]([CH2:9][OH:10])[CH:8]=1.C(N(CC)CC)C.[CH3:62][S:63](Cl)(=[O:65])=[O:64]>ClCCl>[CH3:62][S:63]([O:1][CH2:2][C:3]1[CH:4]=[C:5]([N:11]([CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][O:42][CH2:43][CH2:44][O:45][CH2:46][CH2:47][O:48][CH2:49][CH2:50][C:51]([O:53][CH3:54])=[O:52])[CH3:12])[CH:6]=[C:7]([CH2:9][O:10][S:63]([CH3:62])(=[O:65])=[O:64])[CH:8]=1)(=[O:65])=[O:64]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 68633754Methyl 2-(3,5-bis(hydroxymethyl)phenyl)-5,8,11,14,17,20,23, 26,29,32,35,38-dodecaoxa-2-azahentetracontan-41-oate

Product 1

HCID 86644088Methyl 2-(3,5-bis((methylsulfonyloxy)methyl) phenyl)-5,8,11,14,17,20, 23,26,29,32, 35,38-dodecaoxa-2-azahentetracontan-41-oate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-5 °C

Procedure

To a stirred solution of methyl 2-(3,5-bis(hydroxymethyl)phenyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxa-2-azahentetracontan-41-oate (265d) (71 mg, 0.091 mmol) in anhydrous dichloromethane (1.4 mL) was added triethylamine (0.038 mL, 0.272 mmol). The mixture was cooled to −5° C. and methanesulfonyl chloride (0.018 mL, 0.227 mmol) was added slowly. After stirring for one hour at −5° C. the reaction was quenched with cold water and extracted with cold ethyl acetate. The organic extracts were washed with cold water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give methyl 2-(3,5-bis((methylsulfonyloxy)methyl)phenyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxa-2-azahentetracontan-41-oate. MS (m/z). found 960.2 (M+Na)+. To a mixture of methyl 2-(3,5-bis((methylsulfonyloxy)methyl)phenyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxa-2-azahentetracontan-41-oate (69 mg, 0.074 mmol) and compound 8 (54.1 mg, 0.184 mmol) in anhydrous DMF (0.8 mL) was added potassium carbonate (50.8 mg, 0.368 mmol). The reaction was allowed to stir for 18 hours at room temperature. The reaction was quenched with water and extracted twice with dichloromethane. The remaining aqueous layer was extracted twice with 50% MeOH/CH2Cl2. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by flash silica gel chromatography (5% MeOH/CH2Cl2) followed by preparative reverse phase HPLC (C18 column, eluted with CH3CN/H2O) gave compound 265e (23 mg, 23%). MS (m/z). found 1375.4 (M+Na+H2O)+, 1393.4 (M+Na+2H2O)+.

Workup

  1. customwas quenched with cold water
  2. extractionextracted with cold ethyl acetate
  3. washThe organic extracts were washed with cold water
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fb673e2c25e842aca54110d32b108256
Source dataset
uspto-grants-2014_08
Patent number
US08802667B2

Reaction notes

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