Methylamine → (2S,4R)-2-benzyloxymethyl-4-tritylsulfanyl-pyrrolidine-1-sulfonic acid methylamide

HRID 458361Notes

Reaction equation

HRID 458361 reaction equation
[N:1]1C=CC=C[C:2]=1C.Cl[S:9]([OH:12])(=O)=[O:10].[CH2:13]([O:20][CH2:21][C@@H:22]1[CH2:26][C@@H:25]([S:27][C:28]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:24][NH:23]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O=P(Cl)(Cl)Cl.CN>CCO.COCCOC>[CH3:2][NH:1][S:9]([N:23]1[CH2:24][C@H:25]([S:27][C:28]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:26][C@H:22]1[CH2:21][O:20][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)(=[O:12])=[O:10]

Participants

8

Reactant 5

HCID 6329MethylamineHCID 79752-MethylpyridineHCID 24638Chlorosulfonic acidHCID 24813Phosphorus oxychlorideHCID 69427603(2S,4R)-2-benzyloxymethyl-4-tritylsulfanyl-pyrrolidine

Product 1

HCID 69432323(2S,4R)-2-benzyloxymethyl-4-tritylsulfanyl-pyrrolidine-1-sulfonic acid methylamideYield 28.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
10 °C

Procedure

SO2NHR (via NSO2Cl) Following a procedure described in U.S. Pat. No. 4,868,308: 2.12 ml (21.5 mmol) Alpha-picoline and 0.19 ml (2.8 mmol) chloro sulfonic acid were added at −10° C. to 30 ml 1,2-dimethoxyethane, warmed up to 10° C. and treated with 431 mg (0.93 mmol) of (2S,4R)-2-benzyloxymethyl-4-tritylsulfanyl-pyrrolidine. The reaction was stirred at room temperature over night, treated with 0.32 ml (3.5 mmol) POCl3 and after 4 h at room temperature with 5 ml 8.03 M MeNH2 in EtOH. The reaction was stirred over night and extracted with aqueous 10% KHSO4/EtOAc (3×), the organic phases were washed with 10% NaCl. The crude product was crystallized from CH2Cl2/Et2O at −20° C. to give 147 mg (28%) of (2S,4R)-2-benzyloxymethyl-4-tritylsulfanyl-pyrrolidine-1-sulfonic acid methylamide, mp 140–142° C., MS: 581 (M+Na+).

Workup

  1. stirringThe reaction was stirred over night
  2. extractionextracted with aqueous 10% KHSO4/EtOAc (3×)
  3. washthe organic phases were washed with 10% NaCl
  4. customThe crude product was crystallized from CH2Cl2/Et2O at −20° C.

Sources & evidence

ORD record
ord-206b03d565164da5ab1398821d9ea143
Source dataset
uspto-grants-2007_03
Patent number
US07189756B2

Reaction notes

Loading…