1-Chloroethyl 2-methylpropanoate → (2-Methylpropanoyloxy)ethyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoate

HRID 1919423Notes

Reaction equation

HRID 1919423 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].[CH3:25][CH:26]([CH3:33])[C:27]([O:29][CH:30](Cl)[CH3:31])=[O:28]>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[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][CH2:31][CH2:30][O:29][C:27](=[O:28])[CH:26]([CH3:33])[CH3:25])=[O:13])(=[O:6])=[O:7]

Participants

5

Reactant 2

HCID 131387431-Chloroethyl 2-methylpropanoateHCID 86628870(2R)-4-[(3-Chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoic acid

Product 1

HCID 86628896(2-Methylpropanoyloxy)ethyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoateYield 65%

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 1140TolueneSolvent

Procedure

Following the general procedure for the preparation of acyloxyalkyl/alkoxycarbonyloxyalkyl carboxylic esters from carboxylic acids of Description 22, (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoic acid (11) (13.0 g, 34.3 mmol) dissolved in 300 mL of anhydrous toluene was reacted with 15.4 g (103 mmol) of 1-chloroethyl 2-methylpropanoate (22) in the presence of 23 g (86 mmol) of silver carbonate (Ag2CO3). 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 11 g (65% yield) of the title compound (29a) as a colorless oil. Rf=0.63 (EtOAc/Hxn=1:2). 1H NMR (400 MHz, CDCl3, both diastereomers): δ=1.06-1.23 (m, 12H), 1.53 (d, J=5.6 Hz, 3H), 2.24-2.32 (m, 2H), 2.51-2.65 (m, 1H), 3.21-3.26 (m, 2H), 3.63-3.66 (m, 2H), 3.83-3.85 (2s, 1H), 3.96 (d, J=9.6 Hz, 1H), 4.20-4.24 (2d, J=8.8, 9.2 Hz, 1H), 4.33-4.37 (2d, J=11.2, 11.6 Hz, 1H), 4.60-4.66 (2d, J=11.6, 11.6 Hz, 1H), 6.91-6.95 (m, 1H), 7.30-7.37 (m, 5H) ppm. MS (ESI) m/z 514.90 (M+Na)+.

Workup

  1. customAfter work-up, the crude material was purified by silica gel column chromatography
  2. additiona mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:2) as eluent

Sources & evidence

ORD record
ord-367cfd0e6dd14634a15083687117d40d
Source dataset
uspto-grants-2012_05
Patent number
US08168617B2

Reaction notes

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