Dimethylformamide → HCID 86629054, compound

HRID 1671461Notes

Reaction equation

HRID 1671461 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:20])([CH3:19])[C@@H:11]([O:15][C:16](=[O:18])[CH3:17])[C:12]([OH:14])=[O:13])(=[O:7])=[O:6].C(Cl)(=O)C(Cl)=O.CN(C)C=O.[N:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38]O)[CH:33]=1>ClCCl>[Cl:1][CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:20])([CH3:19])[C@@H:11]([O:15][C:16](=[O:18])[CH3:17])[C:12]([O:14][CH2:38][C:34]1[CH:33]=[N:32][CH:37]=[CH:36][CH:35]=1)=[O:13])(=[O:6])=[O:7]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 75103-PyridinemethanolHCID 65578Oxalyl chlorideHCID 86629055HCID 86629055, compound

Product 1

HCID 86629054HCID 86629054, compoundYield 55.5%

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]-2-acetyloxy-3,3-dimethylbutanoic acid (16) (0.31 g, 0.94 mmol) dissolved in 10 mL of anhydrous dichloromethane (DCM) was reacted with 0.56 mL (1.1 mmol) of oxalyl chloride (2.0 M in DCM) in the presence of a catalytic amount of N,N-dimethylformamide (DMF). After completion of the reaction, a solution of 0.28 mL of 3-pyridylmethanol (0.26 g, 2.3 mmol) in dichloromethane 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 hexane (Hxn) as eluent (EtOAc/Hxn=2:1) to provide 0.22 g (54% yield) of the title compound (38a) as a colorless oil. Rf=0.55 (EtOAc). 1H NMR (400 MHz, CDCl3):): δ=1.03 (s, 3H), 1.05 (s, 3H), 2.10 (s, 3H), 2.22-2.30 (m, 2H), 3.24-3.28 (m, 2H), 3.62-3.66 (m, 2H), 3.92 (d, J=9.2 Hz, 1H), 4.12 (d, J=9.6 Hz, 1H), 4.77 (s, 1H), 5.15-5.22 (m, 2H), 7.30-7.34 (m, 1H), 7.70-7.73 (m, 1H), 8.54-8.59 (m, 2H) ppm. MS (ESI) m/z 422.00 (M+H)+. The analytical data was consistent with 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 hexane (Hxn) as eluent (EtOAc/Hxn=2:1)

Sources & evidence

ORD record
ord-e3776262d8cc48a5bc4909bc3854e3c6
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

Loading…