Sodium methanethiolate → (4R,5R)-4-Fluoromethyl-2,2-dimethyl-5-(4-methylsulfanyl-phenyl)-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 1484418Notes

Reaction equation

HRID 1484418 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][F:14])[C@@H:11]([C:15]2[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][S-:25].[Na+].[Na+].N1CCC[C@H]1C([O-])=O>CS(C)=O.[Cu]I>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][F:14])[C@@H:11]([C:15]2[CH:20]=[CH:19][C:18]([S:25][CH3:24])=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 4378561Sodium methanethiolateHCID 23678551L-Proline sodium saltHCID 117655372(4R,5R)-4-Fluoromethyl-5-(4-iodo-phenyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 117655283(4R,5R)-4-Fluoromethyl-2,2-dimethyl-5-(4-methylsulfanyl-phenyl)-oxazolidine-3-carboxylic acid tert-butyl esterYield 86.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (4R,5R)-4-Fluoromethyl-5-(4-iodo-phenyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (2.4 g, 5.51 mmol) in DMSO (40 mL) is added Sodium thiomethoxide (0.463 g, 6.621 mmol), CuI (0.105 g, 0.552 mmol) and L-proline sodium salt (0.151 g, 1.103 mmol) and heated the mixture at 90° C. for 24 h. Reaction mixture is quenched with water and extracted with ethyl acetate. Organic layer is washed with brine and dried over sodium sulphate, concentrated and purified by CombiFlash using 120 g column with 9.26% ethyl acetate in hexane as an eluent to afford title compound (1.7 g) as faint yellow solid. 1H-NMR (400 MHz, DMSO): δ 1.42 (s, 9H), 1.47 (s, 3H), 1.59 (s, 3H), 2.47 (s, 3H), 3.73-3.79 (m, 1H), 4.37-4.92 (m, 1H), 4.71-4.94 (m, 1H), 5.01 (d, J=7.44 Hz, 1H), 7.27 (d, J=8.28 Hz, 2H), 7.39 (d, J=8.36 Hz, 2H). LC-MS (m/z): M+H=356.2.

Workup

  1. customReaction mixture
  2. customis quenched with water
  3. extractionextracted with ethyl acetate
  4. washOrganic layer is washed with brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. custompurified by CombiFlash

Sources & evidence

ORD record
ord-3beae5bf976f469e8b233c6b2ac0f763
Source dataset
uspto-grants-2016_08
Patent number
US09422236B2

Reaction notes

Loading…