Hydrochloric Acid → (2S,4S)-N-methanesulfonyl-4-dicyclohexylphosphinyl-2-methanesulfonyloxymethylpyrrolidine

HRID 1638409Notes

Reaction equation

HRID 1638409 reaction equation
[CH3:1][S:2]([N:5]1[CH2:9][C@@H:8]([P:10]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)=[O:11])[CH2:7][C@H:6]1[CH2:24][OH:25])(=[O:4])=[O:3].[CH3:26][S:27](Cl)(=[O:29])=[O:28].Cl>N1C=CC=CC=1>[CH3:1][S:2]([N:5]1[CH2:9][C@@H:8]([P:10]([CH:18]2[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]2)([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)=[O:11])[CH2:7][C@H:6]1[CH2:24][O:25][S:27]([CH3:26])(=[O:29])=[O:28])(=[O:3])=[O:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 31297Methanesulfonyl chlorideHCID 13665142(2S,4S)-N-methanesulfonyl-4-dicyclohexylphosphinyl-2-hydroxymethylpyrrolidine

Product 1

HCID 13665144(2S,4S)-N-methanesulfonyl-4-dicyclohexylphosphinyl-2-methanesulfonyloxymethylpyrrolidineYield 74%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

In 20 ml of pyridine was dissolved 1.4 g (3.6 m-mol) of (2S,4S)-N-methanesulfonyl-4-dicyclohexylphosphinyl-2-hydroxymethylpyrrolidine [VIII], and 0.82 g (7.2 m-xol) of methanesulfonyl chloride was added dropwise to the solution under ice-cooling. After stirring the mixture at 0° C. for 3 hours and then at room temperature overnight, 70 ml of 10% hydrochloric acid was added to the mixture under ice-cooling. The mixture was extracted three times with 80 ml of ethyl acetate, and the extract was washed with 30 ml of a saturated solution of sodium hydrogen carbonate and with 30 ml of water and dried over magnesium sulfate. The extract was concentrated under reduced pressure to obtain 1.24 g (yield: 74%) of (2S,4S)-N-methanesulfonyl-4-dicyclohexylphosphinyl-2-methanesulfonyloxymethylpyrrolidine as white crystals. Besides this, 1.88 g (8.52 m-mol) of chlorodiphenylphosphine and 392 mg (17.04 m-mol) of metallic sodium were added to 20 ml of dioxane and the mixture was refluxed in nitrogen atmosphere for 3 hours. After allowing the mixture to stand for cooling, 20 ml of tetrahydrofuran was added to the mixture, and a solution of the previously obtained crystals in 20 ml of dimethylformamide was added dropwise to the mixture at -20° C. to -30° C. lest any air should enter in the reaction system. The mixture was stirred overnight at -20° C. to -30° C. in nitrogen atmosphere, separated from insoluble matters and concentrated under reduced pressure. The residue was extracted three times with 50 ml of ethyl acetate and the extract was washed with 50 ml of water and concentrated under reduced pressure. Using 2.45 g (7.2 m-mol) of 10% hydrogen peroxide, the operation was carried out in the same manner as described in Example 1(e) whereby the title compound was obtained as crystals. Yield 982 mg (80%).

Workup

  1. additionwas added dropwise to the solution under ice-
  2. temperaturecooling
  3. temperaturecooling
  4. extractionThe mixture was extracted three times with 80 ml of ethyl acetate
  5. washthe extract was washed with 30 ml of a saturated solution of sodium hydrogen carbonate and with 30 ml of water
  6. dry with materialdried over magnesium sulfate
  7. concentrationThe extract was concentrated under reduced pressure

Sources & evidence

ORD record
ord-699b320b72bb426caa5d6444025ffcea
Source dataset
uspto-grants-1989_11
Patent number
US04879389

Reaction notes

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