4-Toluenesulfonyl chloride → HCID 58150642, compound

HRID 1184603Notes

Reaction equation

HRID 1184603 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

(2S,4R)-tert-Butyl 4-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate (500 mg, 2.3 mmol) in pyridine (20 mL) was cooled to 0° C. and treated with a solution of p-toluenesulfonyl chloride (483 mg, 2.53 mmol) in pyridine (5 mL) added over a period of 1 hour. The reaction was allowed to slowly warm to ambient temperature with continued stirring for 48 hours. The resulting material was triturated with ethyl acetate and purified by flash chromatography on a 12 g silica gel column, eluting with 5% ethyl acetate/hexanes for 3 minutes followed by a gradient to 100% ethyl acetate over 20 minutes to afford the title compound as an oil (397 mg; 64%). 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. additionadded over a period of 1 hour
  2. customThe resulting material was triturated with ethyl acetate
  3. custompurified by flash chromatography on a 12 g silica gel column
  4. washeluting with 5% ethyl acetate/hexanes for 3 minutes
  5. waitfollowed by a gradient to 100% ethyl acetate over 20 minutes

Sources & evidence

ORD record
ord-8a07ac8635594343bffbad71db110bf1
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

Loading…