Ethanol → HCID 86629019, compound

HRID 1671421Notes

Reaction equation

HRID 1671421 reaction equation
[O:1]=[C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][S:15]([O:18][CH2:19][C:20]([CH3:34])([CH3:33])[C@@H:21]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:22]([OH:24])=[O:23])(=[O:17])=[O:16].[C:35](Cl)(=O)[C:36](Cl)=O.C(O)C.N1C=CC=CC=1>ClCCl>[O:11]=[C:4]1[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:2](=[O:1])[N:3]1[CH2:12][CH2:13][CH2:14][S:15]([O:18][CH2:19][C:20]([CH3:34])([CH3:33])[C@@H:21]([O:25][CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:22]([O:24][CH2:35][CH3:36])=[O:23])(=[O:16])=[O:17]

Participants

6

Reactant 4

HCID 702EthanolHCID 1049PyridineHCID 65578Oxalyl chlorideHCID 86628888HCID 86628888, compound

Product 1

HCID 86629019HCID 86629019, compoundYield 84.5%

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-(1,3-dioxobenzo[c]azolin-2-yl)propyl]sulfonyloxy}-3,3-dimethyl-2-(phenylmethoxy)butanoic acid (20) (0.8 g, 1.6 mmol) was dissolved in 20 mL of anhydrous dichloromethane (DCM) and reacted with 0.96 mL (1.92 mmol) of oxalyl chloride (2.0 M in DCM). After completion of the reaction, a solution of 2.0 mL (1.58 g, 34.3 mmol) of ethanol (EtOH) and 0.14 mL (0.127 g, 1.6 mmol) of pyridine in 10 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 hexane (Hxn) (EtOAc/Hxn=1:2) as eluent to provide 0.7 g (83% yield) of the title compound (22a) as a colorless oil. Rf=0.64 (EtOAc/Hxn=1:2). 1H NMR (400 MHz, CDCl3): δ=1.04 (s, 3H), 1.05 (s, 3H), 1.31 (t, J=6.8 Hz, 3H), 2.18-2.25 (m, 2H), 3.12-3.17 (m, 2H), 3.80 (t, J=6.8 Hz, 2H), 3.83 (s, 1H), 3.96 (d, J=8.8 Hz, 1H), 4.18-4.24 (m, 3H), 4.36 (d, J=11.2 Hz, 1H), 4.60 (d, J=11.6 Hz, 1H), 7.32-7.33 (m, 5H), 7.72-7.75 (m, 2H), 7.84-7.86 (m, 2H) ppm. MS (ESI) m/z 518.16 (M+H)+, 540.11 (M+Na)+. 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) (EtOAc/Hxn=1:2) as eluent

Sources & evidence

ORD record
ord-1a2ecadd2c954a0cac3ed70633107a4c
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

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