4-Toluenesulfonyl chloride → HCID 54480540, compound

HRID 1740475Notes

Reaction equation

HRID 1740475 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@@H:9]1[CH2:14][O:15][C:16]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1)[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:39]1([CH3:49])[CH:44]=[CH:43][C:42]([S:45](Cl)(=[O:47])=[O:46])=[CH:41][CH:40]=1>N1C=CC=CC=1.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][S:45]([C:42]2[CH:43]=[CH:44][C:39]([CH3:49])=[CH:40][CH:41]=2)(=[O:47])=[O:46])[CH2:10][C@@H:9]1[CH2:14][O:15][C:16]([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)[C:25]1[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 54152206HCID 54152206, compound

Product 1

HCID 54480540HCID 54480540, compoundYield 89.3%

Reagents, catalysts & solvents 1

HCID 21875418Pyridine methylene chlorideSolvent

Conditions

Temperature
0 °C

Procedure

(2R,4R)-1-(tert-Butyloxycarbonyl)-2-(4,4'-Dimethoxytrityl) oxymethyl-4-hydroxypyrrolidine 38 (8.09 g, 20.27 mmol) was dissolved in dry pyridine/CH2Cl2 (2:1, 200 ml) and chilled in an ice bath under argon atmosphere. To this cold solution was added TEA (3.03 g, 30 mmol) followed by p-toluenesulphonyl chloride (5.7 g, 30 mmol). The reaction mixture was allowed to stir at 0° C. for 3 h and below 30° C. for 8 h. The reaction mixture was evaporated to dryness, partitioned between EtOAc (200 ml) and 5% NaHCO3 solution (100 ml), and extracted in EtOAc. The EtOAc extract was washed with water (100 ml) and brine (100 ml), dried and evaporated to dryness. The crude product was purified by flash chromatography over silica gel using hexane→EtOAc as the eluent. The pure fractions were pooled together and evaporated to give 12.2 g (89%) of an orange oil. 1HNMR (CDCl3): 1.45 (s, 9H, Boc), 1.90 (dd, 1H), 2.34 (m, 1H), 2.40 (s, 3H, CH3), 3.40-3.62 (m, 3H), 3.74 (s, 6H, 2.OCH3), 4.00 (m, 2H), 4.28 (bs, 1H), 4.44 (m, 1H), 6.82 (d, 4H, Ph), and 7.26-8.00 (m, 13H, Ph).

Workup

  1. temperaturechilled in an ice bath under argon atmosphere
  2. customThe reaction mixture was evaporated to dryness
  3. custompartitioned between EtOAc (200 ml) and 5% NaHCO3 solution (100 ml)
  4. extractionextracted in EtOAc
  5. extractionThe EtOAc extract
  6. washwas washed with water (100 ml) and brine (100 ml)
  7. customdried
  8. customevaporated to dryness
  9. customThe crude product was purified by flash chromatography over silica gel
  10. customevaporated

Sources & evidence

ORD record
ord-844a3cb0de064022a8b8a7d4eba9f1ed
Source dataset
uspto-grants-1999_10
Patent number
US05969135

Reaction notes

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