Pyridine → HCID 86629046, compound

HRID 1671452Notes

Reaction equation

HRID 1671452 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.[C:33]1([C@@H:39](O)[CH3:40])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.N1C=CC=CC=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][C@H:39]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH3:40])=[O:13])(=[O:7])=[O:6]

Participants

6

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 4431351-Phenylethanol, (S)-HCID 86628873HCID 86628873, compound

Product 1

HCID 86629046HCID 86629046, compoundYield 75%

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 (S)-(−)-1-phenylethanol (0.23 g, 1.8 mmol) and 0.10 mL of pyridine (96 mg, 1.2 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=1:2) to provide 0.46 g (75% yield) of the title compound (35a) as a colorless oil. Rf=0.54 (EtOAc/Hex=1:2). 1H NMR (400 MHz, CDCl3): δ=1.03 (s, 3H), 1.06 (s, 3H), 1.61 (d, J=6.8 Hz, 3H), 2.24-2.30 (m, 2H), 3.18-3.23 (m, 2H), 3.63-3.66 (m, 2H), 3.81-3.82 (m, 4H), 3.95 (d, J=9.6 Hz, 1H), 4.19 (d, J=8.8 Hz, 1H), 4.26 (d, J=11.6 Hz, 1H), 4.51 (d, J=10.8 Hz, 1H), 6.01 (q, J=6.8 Hz, 1H), 6.83 (d, J=8.8 Hz, 2H), 7.18 (d, J=8.8 Hz, 2H), 7.35-7.39 (m, 5H) ppm. D.e.>98% (by 1H NMR-spectroscopy, 400 MHz, CDCl3). MS (ESI) m/z 535.18 (M+Na)+. The analytical data was consistant 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=1:2)

Sources & evidence

ORD record
ord-18e0a855f7794b92b3a5edf295b018b3
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

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