3-Pyridinemethanol → HCID 86629051, compound

HRID 1671458Notes

Reaction equation

HRID 1671458 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:26])([CH3:25])[C@@H:11]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)[C:12]([OH:14])=[O:13])(=[O:7])=[O:6].C(Cl)(=O)C(Cl)=O.[N:33]1[CH:38]=[CH:37][CH:36]=[C:35]([CH2:39]O)[CH:34]=1>ClCCl>[Cl:1][CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:26])([CH3:25])[C@@H:11]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)[C:12]([O:14][CH2:39][C:35]1[CH:34]=[N:33][CH:38]=[CH:37][CH:36]=1)=[O:13])(=[O:7])=[O:6]

Participants

5

Reactant 3

HCID 75103-PyridinemethanolHCID 65578Oxalyl chlorideHCID 86628873HCID 86628873, compound

Product 1

HCID 86629051HCID 86629051, compoundYield 50%

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-[(4-methoxyphenyl)methoxy]-3,3-dimethylbutanoic acid (13) (0.50 g, 1.2 mmol) dissolved in 20 mL of anhydrous dichloromethane (DCM) was reacted with 0.7 mL (1.4 mmol) of oxalyl chloride (2.0 M in DCM). After completion of the reaction, a solution of 0.28 mL of 3-pyridylmethanol (0.28 g, 2.5 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=1:1) to provide 0.30 g (50% yield) of the title compound (37a) as a colorless oil. Rf=0.34 (EtOAc/Hex=1:1). 1H NMR (400 MHz, CDCl3): δ=1.01 (s, 6H), 2.24-2.31 (m, 2H), 3.20-3.25 (m, 2H), 3.64-3.67 (m, 2H), 3.81 (s, 3H), 3.85 (s, 1H), 3.94 (d, J=9.6 Hz, 1H), 4.19 (d, J=8.8 Hz, 1H), 4.29 (d, J=10.8 Hz, 1H), 4.52 (d, J=11.2 Hz, 1H), 5.20 (s, 2H), 6.85 (d, J=8.8 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 7.31-7.34 (m, 1H), 7.71-7.73 (m, 1H), 8.60-8.66 (m, 2H) ppm. MS (ESI) m/z 500.01 (M+H)+. The analytical data was 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 hexane (Hxn) as eluent (EtOAc/Hxn=1:1)

Sources & evidence

ORD record
ord-17bbe3aa18c84c4c94d15f3a26982abd
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

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