Pyridine → (1S)-1,3-Dimethyl-2-oxobutyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(1,1,2,2-tetramethyl-1-silapropoxy)butanoate

HRID 1919426Notes

Reaction equation

HRID 1919426 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][Si:16]([CH3:22])([CH3:21])[C:17]([CH3:20])([CH3:19])[CH3:18])[C:12]([OH:14])=[O:13])(=[O:7])=[O:6].C(Cl)(=O)C(Cl)=O.O[C@H:32]([C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])[CH3:33].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][Si:16]([CH3:22])([CH3:21])[C:17]([CH3:19])([CH3:18])[CH3:20])[C:12]([O:14][C@@H:32]([CH3:33])[C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])=[O:13])(=[O:7])=[O:6]

Participants

6

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 45085102(2S)-2-hydroxy-4-methylpentan-3-oneHCID 86628876(2R)-4-[(3-Chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(1,1,2,2-tetramethyl-1-silapropoxy)butanoic acid

Product 1

HCID 86628899(1S)-1,3-Dimethyl-2-oxobutyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(1,1,2,2-tetramethyl-1-silapropoxy)butanoateYield 36%

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-(1,1,2,2-tetramethyl-1-silapropoxy)butanoic acid (15) (2.0 g, 5.0 mmol) dissolved in 25 mL of anhydrous dichloromethane (DCM) was reacted with 0.90 mL (1.31 g, 10 mmol) of oxalyl chloride. Upon completion of the reaction, a solution of 2 mL (1.2 g, 10.0 mmol) of (2S)-2-hydroxy-4-methylpentan-3-one (synthesized following procedures according to Gallop et al., U.S. Pat. No. 6,927,036) and 0.85 mL of pyridine (0.79 g, 10.0 mmol) in 20 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=1:9) as eluent to provide 0.9 g (36% yield) of the title compound (30a) as a colorless oil. Rf=0.39 (EtOAc/Hxn=1:4). 1H NMR (400 MHz, CDCl3): δ=0.05 (s, 3H), 0.10 (s, 3H), 0.94 (s, 9H), 1.09 (s, 6H), 1.12 (d, J=7.2 Hz, 3H), 1.19 (d, J=7.2 Hz, 3H), 1.46 (d, J=7.2 Hz, 3H), 2.32-2.39 (m, 2H), 2.83 (sept., J=7.2 Hz, 1H), 3.31-3.35 (m, 2H), 3.69-3.72 (m, 2H), 4.10-4.13 (m, 3H), 5.24 (q, J=7.2 Hz, 1H) ppm. MS (ESI) m/z 501.09 (M+H)+, 523.03 (M+Na)+. The analytical data was consistent with the proposed structure.

Workup

  1. customUpon 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=1:9) as eluent

Sources & evidence

ORD record
ord-8ddf3d8250374de8937af2564c0d5c28
Source dataset
uspto-grants-2012_05
Patent number
US08168617B2

Reaction notes

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