Methanesulfonic Acid → HCID 87832739, compound

HRID 1006806Notes

Reaction equation

HRID 1006806 reaction equation
C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:27][S:28]([OH:31])(=[O:30])=[O:29].O[C@H:33]1[CH2:37][N:36]([S:38]([C:41]2[CH:50]=[CH:49][C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH:42]=2)(=[O:40])=[O:39])[C@H:35]([CH2:51][N:52]2[C:60](=[O:61])[C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[C:53]2=[O:62])[CH2:34]1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1.C1(C)C=CC=CC=1.C1COCC1.CCOC(C)=O.O>[O:61]=[C:60]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[C:53](=[O:62])[N:52]1[CH2:51][C@H:35]1[N:36]([S:38]([C:41]2[CH:50]=[CH:49][C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH:42]=2)(=[O:40])=[O:39])[CH2:37][C@H:33]([O:29][S:28]([CH3:27])(=[O:31])=[O:30])[CH2:34]1

Participants

10

Reactant 5

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 69432047HCID 69432047, compound

Product 1

HCID 87832739HCID 87832739, compoundYield 90%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
80 °C

Procedure

3.0 ml (21.7 mmol, 1.2 eq) triethylamine and 6.05 g (22.6 mmol, 1.2 eq) triphenylphosphine were added to a solution of 1.42 ml (21.7 mmol, 1.25 eq) methanesulfonic acid in 60 ml toluene, successively followed by a solution of 7.9 g (18.1 mmol) (2S,4R)-2-[4-hydroxy-1-(naphthalene-2-sulfonyl)-pyrrolidin-2-ylmethyl]-isoindole-1,3-dione in 80 ml toluene/THF (5/3) and 5.06 ml (23.6 mmol, 1.3 eq) DIAD. The suspension was heated to 80° C. for 6 h and stirred at room temperature overnight. After diluting the mixture with EtOAc and water, the phases were separated, and the inorganic one was extracted with EtOAc and CH2Cl2, the combined organic phases were washed with 1M KHSO4 and brine, dried over Na2SO4 and evaporated. Column chromatography with a gradient of CH2Cl2: EtOAc 4:1 to 1:1 yielded 8.3 g (90%) of (3R,5S)-methanesulfonic acid 5-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-1-(naphthalene-2-sulfonyl)-pyrrolidin-3-yl ester as white crystals.

Workup

  1. customthe phases were separated
  2. extractionthe inorganic one was extracted with EtOAc and CH2Cl2
  3. washthe combined organic phases were washed with 1M KHSO4 and brine
  4. dry with materialdried over Na2SO4
  5. customevaporated

Sources & evidence

ORD record
ord-d98aeb8f991b4017a761eebf03942032
Source dataset
uspto-grants-2004_09
Patent number
US06790860B2

Reaction notes

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