(Diethylamino)sulfur trifluoride → (4R,5R)-4-Fluoromethyl-5-(4-fluoromethylsulfanyl-phenyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 1484420Notes

Reaction equation

HRID 1484420 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]([S:21]([CH3:23])=O)=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:25])[CH3:24])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(S(F)(F)[F:32])CC>C(Cl)Cl>[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:21][CH2:23][F:32])=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:25])[CH3:24])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 117662128(4R,5R)-4-Fluoromethyl-5-(4-methanesulfinyl-phenyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 117662126(4R,5R)-4-Fluoromethyl-5-(4-fluoromethylsulfanyl-phenyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl esterYield 56.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (4R,5R)-4-Fluoromethyl-5-(4-methanesulfinyl-phenyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1.0 g, 2.69 mmol) in DCM (50 mL) is cooled to 0° C. followed by addition of SbCl3 (0.018 g, 0.081 mmol) and DAST (0.6 mL, 4.582 mmol). The resulting reaction mixture is stirred at RT for 16 h. After completion reaction mixture is quenched with aqueous bicarbonate solution and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, concentrated and purified by combi-flash chromatography (12 g column) using 8% ethyl acetate in n-Hexane as an eluent to afford title compound (564 mg) as colorless oil. 1H-NMR (400 MHz, DMSO): δ 1.41 (s, 9H), 1.48 (s, 3H), 1.61 (s, 3H), 377-.382 (m, 1H), 4.42-4.53 (m, 1H), 4.76-4.92 (m, 1H), 5.06 (d, J=7.36 Hz, 1H), 5.99 (d, J=52.32 Hz, 2H), 7.46-7.51 (m, 4H). LC-MS (m/z): M+H=374.1.

Workup

  1. customThe resulting reaction mixture
  2. customAfter completion reaction mixture
  3. customis quenched with aqueous bicarbonate solution
  4. extractionextracted with ethyl acetate
  5. dry with materialOrganic layer is dried over sodium sulphate
  6. concentrationconcentrated
  7. custompurified by combi-flash chromatography (12 g column)

Sources & evidence

ORD record
ord-97ccda6119dc46468bef70c46914c9fd
Source dataset
uspto-grants-2016_08
Patent number
US09422236B2

Reaction notes

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