Methanesulfonic Acid → (4S,2S)-4-Methanesulfonyloxy-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid methylester

HRID 458301Notes

Reaction equation

HRID 458301 reaction equation
[S:1]([O-:5])(=[O:4])(=[O:3])[CH3:2].CS(O)(=O)=O.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:37][O:38][C:39]([C@@H:41]1[CH2:45][C@@H:44](O)[CH2:43][N:42]1[S:47]([C:50]1[CH:59]=[CH:58][C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:51]=1)(=[O:49])=[O:48])=[O:40].N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1(C)C=CC=CC=1.CCOC(C)=O.CCCCCC.O>[CH3:37][O:38][C:39]([C@@H:41]1[CH2:45][C@H:44]([O:3][S:1]([CH3:2])(=[O:5])=[O:4])[CH2:43][N:42]1[S:47]([C:50]1[CH:59]=[CH:58][C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:51]=1)(=[O:49])=[O:48])=[O:40]

Participants

10

Reactant 6

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 85257MethanesulfonateHCID 7987003(2S,4R)-4-Hydroxy-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid methyl ester

Product 1

HCID 11441344(4S,2S)-4-Methanesulfonyloxy-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid methylesterYield 86%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
80 °C

Procedure

Via Mesylate: A biphasic solution of 13.9 ml (215 mmol) methanesulfonic acid, 29.8 ml (215 mmol) triethylamine and 58.7 g (224 mmol) triphenylphosphine in 150 ml toluene was added to a suspension of 60 g (179 mmol) (2S,4R)-4-hydroxy-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid methyl ester in 300 ml toluene which was stirred mechanically. After adding 44.9 ml (233 mmol) of diisopropyl azodicaboxylate (exothermic!) the solution was heated for 2.5 h at 80° C. 300 ml water was added at room temperature and extracted with EtOAc (3×300 ml). The organic phase was washed with aqueous 10% KHSO4 (2×100 ml), 10% NaCl (2×150 ml) dried over Na2SO4 and evaporated to give 180 g of crude product. Flash chromatography (EtOAc/hexane 1:1) gave 63.7 g (86%) of (4S, 2S)-4-methanesulfonyloxy-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid methylester.

Workup

  1. extractionextracted with EtOAc (3×300 ml)
  2. washThe organic phase was washed with aqueous 10% KHSO4 (2×100 ml), 10% NaCl (2×150 ml)
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customto give 180 g of crude product

Sources & evidence

ORD record
ord-22f9569d0d7b409583acef8cf4e056a9
Source dataset
uspto-grants-2007_03
Patent number
US07189756B2

Reaction notes

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