Chloromethyl phenylacetate → (2-Phenylacetyloxy)methyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoate

HRID 1919420Notes

Reaction equation

HRID 1919420 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:25]1([CH2:31][C:32]([O:34][CH2:35]Cl)=[O:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>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][CH2:35][O:34][C:32](=[O:33])[CH2:31][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)=[O:13])(=[O:6])=[O:7]

Participants

5

Reactant 2

HCID 11286872Chloromethyl phenylacetateHCID 86628870(2R)-4-[(3-Chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoic acid

Product 1

HCID 86628893(2-Phenylacetyloxy)methyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoateYield 64.2%

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) (0.5 g, 1.3 mmol) dissolved in 10 mL of anhydrous toluene was reacted with 1.1 g (4.0 mmol) of chloromethyl 2-phenylacetate in the presence of 0.44 g (1.6 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 0.44 g (64% yield) of the title compound (28a) as a colorless oil. Rf=0.47 (EtOAc/Hxn=1:2). 1H NMR (400 MHz, CDCl3): δ=0.97 (s, 3H), 0.99 (s, 3H), 2.24-2.30 (m, 2H), 3.20-3.24 (m, 2H), 3.62-3.65 (m, 2H), 3.68 (s, 2H), 3.84 (s, 1H), 3.91 (d, J=9.2 Hz, 1H), 4.15 (d, J=9.6 Hz, 1H), 4.28 (d, J=10.8 Hz, 1H), 4.53 (d, J=11.2 Hz, 1H), 5.78 (d, J=5.6 Hz, 1H), 5.87 (d, J=5.6 Hz, 1H), 7.25-7.38 (m, 10H) ppm. MS (ESI) m/z 548.99 (M+Na)+. The analytical data was consistent with the proposed structure.

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-d60dbc053dbc467a9b31bf98f39180be
Source dataset
uspto-grants-2012_05
Patent number
US08168617B2

Reaction notes

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