Water → 1-benzyl 4-methyl (2S)-2-[benzyl((2S)-2-hydroxy-3-[(4-methylphenyl)sulfonyl]oxypropyl)amino]succinate

HRID 535046

Reaction equation

HRID 535046 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C@H:13]2[O:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C[Al](C)C.[CH3:20][O:21][C:22](=[O:43])[CH2:23][C@H:24]([NH:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26].C(=O)=O.CC(C)=O.[F-].[Na+].O>C(Cl)Cl.C1(C)C=CC=CC=1>[CH2:36]([N:35]([CH2:14][C@H:13]([OH:15])[CH2:12][O:11][S:8]([C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=1)(=[O:9])=[O:10])[C@@H:24]([CH2:23][C:22]([O:21][CH3:20])=[O:43])[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

9

Reactant 6

HCID 962WaterHCID 5235Sodium FluorideHCID 153296Oxiranemethanol, 4-methylbenzenesulfonate, (S)-HCID 16682925TrimethylaluminumHCID 18522661Acetone cardiceHCID 67303755(S)-2-benzylamino-succinic acid 1-benzyl ester 4-methyl ester

Product 1

HCID 873486681-benzyl 4-methyl (2S)-2-[benzyl((2S)-2-hydroxy-3-[(4-methylphenyl)sulfonyl]oxypropyl)amino]succinateYield 91.8%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of (2S)-(+)-glycidyl tosylate (23.0 g, 0.101 mol) in 500 mL of methylene chloride was added 2.00 M of trimethylaluminum in toluene (50.4 mL) at −78 Celsius, under an atmosphere of nitrogen. After stirred at −78 Celsius for 10 min, to the mixture was added a solution of (S)-2-benzylamino-succinic acid 1-benzyl ester 4-methyl ester (30.0 g, 0.0916 mol) in 150 mL of methylene chloride. The resulting reaction mixture was stirred at −78 Celsius for 30 min. The dry ice-acetone bath was changed to an ice-water bath to warm the mixture up to 0 Celsius. The mixture was stirred at 0 Celsius for 30 min. To the reaction mixture was added sodium fluoride (16.2 g, 0.385 mol) followed by water (10.4 mL, 0.577 mol) at 0 Celsius. The resulting suspension was rapidly stirred for 1 h at 0 Celsius and filtered through a short column of celite and the column was subsequently washed with 600 mL of methylene chloride. The combined filtrates were dried over sodium sulfate, concentrated to dry and purified by column purification (eluting with 0 to 20% EtOAc in hexane) to yield the titled compound (46.7 g, 91.7%). MS (ESI): (M+H)+=556.2.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at −78 Celsius for 30 min
  3. temperatureto warm the mixture up to 0 Celsius
  4. stirringThe mixture was stirred at 0 Celsius for 30 min
  5. stirringThe resulting suspension was rapidly stirred for 1 h at 0 Celsius
  6. filtrationfiltered through a short column of celite
  7. washthe column was subsequently washed with 600 mL of methylene chloride
  8. dry with materialThe combined filtrates were dried over sodium sulfate
  9. concentrationconcentrated
  10. customto dry
  11. custompurified by column purification (eluting with 0 to 20% EtOAc in hexane)

Sources & evidence

ORD record
ord-2f6ffbcd435a4f7da3859880e24c9c1e
Source dataset
uspto-grants-2014_10
Patent number
US08853243B2

Linked notes

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