Pyridine → (N,N-Dimethylcarbamoyl)methyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoate

HRID 1671456Notes

Reaction equation

HRID 1671456 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:24])([CH3:23])[C@@H:11]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:12]([OH:14])=[O:13])(=[O:7])=[O:6].C(Cl)(=O)C(Cl)=O.O[CH2:32][C:33]([N:35]([CH3:37])[CH3:36])=[O:34].N1C=CC=CC=1>ClCCl>[Cl:1][CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:24])([CH3:23])[C@@H:11]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:12]([O:14][CH2:32][C:33](=[O:34])[N:35]([CH3:37])[CH3:36])=[O:13])(=[O:6])=[O:7]

Participants

6

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 128746822-Hydroxy-N,N-dimethylacetamideHCID 86628870(2R)-4-[(3-Chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoic acid

Product 1

HCID 86629049(N,N-Dimethylcarbamoyl)methyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoateYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Following the general procedure for the preparation of carboxylic esters from carboxylic acids of Description 15, (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoic acid (11) (1.1 g, 2.90 mmol) dissolved in 40 mL of anhydrous dichloromethane (DCM) was reacted with 1.74 mL (3.48 mmol) of oxalyl chloride (2.0 M in DCM). After completion of the reaction, an aliquot (ca. 1.45 mmol) of the acid chloride was reacted with 455 mg (4.41 mmol) of 2-hydroxy-N,N-dimethylacetamide (36b) and 352 μL mL of pyridine (344 mg, 4.35 mmol) in 10 mL of anhydrous dichloromethane (DCM). After work-up, the crude material was purified by silica gel column chromatography using mixtures of ethyl acetate (EtOAc) and hexane (Hxn) as eluent (EtOAc/Hxn=2:3→EtOAc/Hxn=1:1) to provide 200 mg (30% yield) of the title compound (36c) as an opaque, viscous oil. Rf=0.28 (EtOAc/Hxn=1:1). MS (ESI) m/z 464.2 (M+H)+, 486.1 (M+Na)+.

Workup

  1. customAfter completion of the reaction
  2. customAfter work-up, the crude material was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-1b063c1007cb4ce3921c8d8093134176
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

Loading…