Pyridine → 2-(Dimethylamino)ethyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoate

HRID 1671437Notes

Reaction equation

HRID 1671437 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:25](Cl)(=O)[C:26](Cl)=O.[N:31]1[CH:36]=CC=C[CH:32]=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][CH2:25][CH2:26][N:31]([CH3:36])[CH3:32])=[O:13])(=[O:6])=[O:7]

Participants

5

Reactant 3

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

Product 1

HCID 866290322-(Dimethylamino)ethyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoateYield 50.2%

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, 3.1 mmol) dissolved in 30 mL of anhydrous dichloromethane (DCM) was reacted with 1.8 mL (3.6 mmol) of oxalyl chloride (2.0 M in DCM). After completion of the reaction, a solution of (2-dimethylamino)ethanol (0.55 g, 6.2 mmol) and 0.50 mL of pyridine (0.49 g, 6.2 mmol) in 20 mL of anhydrous dichloromethane (DCM) was added to the acid chloride. After work-up, the crude material was purified by silica gel column chromatography using a mixture of ethyl acetate (EtOAc) and methanol (MeOH) as eluent (EtOAc/MeOH=9:1) to provide 0.7 g (50% yield) of the title compound (28a) as a colorless oil. Rf=0.23 (EtOAc/MeOH=9:1). 1H NMR (400 MHz, CDCl3): δ=1.08 (s, 3H), 1.09 (s, 3H), 2.28-2.30 (m, 8H), 2.57-2.60 (m, 2H), 3.22-3.26 (m, 2H), 3.64 (t, J=6.0 Hz, 2H), 3.88 (s, 1H), 4.02 (d, J=9.2 Hz, 1H), 4.21 (d, J=9.6 Hz, 1H), 4.27-4.32 (m, 1H), 4.32 (d, J=11.2 Hz, 1H), 4.65 (d, J=11.6 Hz, 1H), 7.30-7.35 (m, 5H) ppm. MS (ESI) m/z 450.04 (M+H)+. The analytical data is consistent with the proposed structure.

Workup

  1. customAfter completion of the reaction
  2. customAfter work-up, the crude material was purified by silica gel column chromatography
  3. additiona mixture of ethyl acetate (EtOAc) and methanol (MeOH) as eluent (EtOAc/MeOH=9:1)

Sources & evidence

ORD record
ord-3898acb8ec954d0da268226a3a436b36
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

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