4-Toluenesulfonyl chloride → HCID 58150642, compound

HRID 240462Notes

Reaction equation

HRID 240462 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([CH2:14][OH:15])[CH2:3]1.[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1>N1C=CC=CC=1>[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@H:4]([CH2:14][O:15][S:22]([C:19]2[CH:20]=[CH:21][C:16]([CH3:26])=[CH:17][CH:18]=2)(=[O:24])=[O:23])[CH2:3]1

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 11275979N-Boc-trans-4-hydroxy-L-prolinol

Product 1

HCID 58150642HCID 58150642, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

tert-Butyl (2S,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate (500 mg; 2.3 mmol) in pyridine (20 mL) was cooled to 0° C. To this cooled solution was added a solution of p-toluenesulfonyl chloride (483 mg, 2.53 mmol) in pyridine (5 mL) over a period of 1 hour. The reaction mixture was allowed to slowly warm to ambient temperature and stirring was continued at ambient for 48 hours. The volatiles were removed in vacuo, and the residue was redissolved in toluene and concentrated again in vacuo. The crude material was triturated with ethyl acetate. This was further purified by chromatography on a 12 g silica gel column eluted with 5% ethyl acetate/hexanes for 3 minutes and then eluted with a gradient to 100% ethyl acetate over 20 minutes. The title compound was isolated as an oil (397 mg; 64% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 7.82-7.69 (m, 2H), 7.48 (d, J=7.9 Hz, 2H), 4.92 (d, J=2.8 Hz, 1H), 4.23-3.82 (m, 4H), 3.12 (dd, J=25.5, 13.9 Hz, 2H), 2.42 (d, J=3.6 Hz, 3H), 1.87 (d, J=20.3 Hz, 2H), 1.35 (dd, J=23.0, 13.0 Hz, 9H).

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe residue was redissolved in toluene
  3. concentrationconcentrated again in vacuo
  4. customThe crude material was triturated with ethyl acetate
  5. customThis was further purified by chromatography on a 12 g silica gel column
  6. washeluted with 5% ethyl acetate/hexanes for 3 minutes
  7. washeluted with a gradient to 100% ethyl acetate over 20 minutes

Sources & evidence

ORD record
ord-f3e3b75e2be2470188bbeaf03e50a317
Source dataset
uspto-grants-2014_02
Patent number
US08648074B2

Reaction notes

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