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

HRID 1671430Notes

Reaction equation

HRID 1671430 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(Cl)(=O)C(Cl)=O.[CH:31](O)([CH3:33])[CH3:32].N1C=CC=CC=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][CH:31]([CH3:33])[CH3:32])=[O:13])(=[O:6])=[O:7]

Participants

6

Reactant 4

HCID 1049PyridineHCID 3776IsopropanolHCID 65578Oxalyl chlorideHCID 86628870(2R)-4-[(3-Chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoic acid

Product 1

HCID 86629024Isopropyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoateYield 76.3%

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) (0.73 g, 1.9 mmol) dissolved in 20 mL of anhydrous dichloromethane (DCM) was reacted with 1.1 mL (2.2 mmol) of oxalyl chloride (2.0 M in DCM). After completion of the reaction, a solution of 2 mL (1.57 g, 26.1 mmol) of isopropanol (iPrOH) and 0.16 mL of pyridine (0.15 g, 1.9 mmol) 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 0.61 g (75% yield) of the title compound (25a) as a colorless oil. Rf=0.67 (EtOAc/Hxn=1:2). 1H NMR (400 MHz, CDCl3): δ=1.06 (s, 3H), 1.08 (s, 3H), 1.30-1.32 (m, 3H), 2.25-2.32 (m, 2H), 3.65 (t, J=5.6 Hz, 2H), 3.81 (s, 1H), 3.98 (d, J=9.2 Hz, 1H), 4.23 (d, J=9.2 Hz, 1H), 4.35 (d, J=11.2 Hz, 1H), 4.62 (d, J=11.2 Hz, 1H), 5.14 (m, 1H), 7.33-7.36 (m, 5H) ppm. MS (ESI) m/z 420.94 (M+H)+, 442.95 (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-773d5871327d4a7e9257d5c961dbdd22
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

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