(Diethylamino)sulfur trifluoride → (2R,5R)-4-Benzyl-5-fluoromethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475440Notes

Reaction equation

C(N(S(F)(F)[F:7])CC)C.[C:10]([O:14][C:15]([N:17]1[CH2:22][C@H:21]([CH2:23]O)[N:20]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:19][C@H:18]1[CH3:32])=[O:16])([CH3:13])([CH3:12])[CH3:11].C(=O)([O-])O.[Na+]>C(Cl)Cl>[C:10]([O:14][C:15]([N:17]1[CH2:22][C@H:21]([CH2:23][F:7])[N:20]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:19][C@H:18]1[CH3:32])=[O:16])([CH3:13])([CH3:12])[CH3:11]

Participants

Conditions

Temperature: -78 °C

Procedure

To a stirred solution of diethylaminosulfur trifluoride (0.32 mL, 0.393 g, 2.44 mmol) in DCM (2 mL) at −78° C. under nitrogen was added a solution of (2R,5R)-4-benzyl-5-hydroxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.651 g, 2.03 mmol) in DCM (6 mL). Mixture was stirred at −78° C. for 0.5 h then at 20° C. for 3 h. Mixture was poured into saturated aqueous sodium hydrogen carbonate (100 mL) and ice (20 g) then extracted with DCM (3×50 mL). Combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography (SiO2; gradient elution with 0-40% Et2O in 40-60 petroleum ether) gave the title compound (0.393 g) as an oil. MS: [M+H]+=323.

Workup

waitat 20° C. for 3 h
extractionthen extracted with DCM (3×50 mL)
dry with materialCombined organic extracts were dried (Na2SO4)
customevaporated in vacuo
customto give an oil
washChromatography (SiO2; gradient elution with 0-40% Et2O in 40-60 petroleum ether)

Sources & evidence

ORD record: ord-b77450b5ce4a4207934895b3cb56c5f7
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018214B2

Reaction notes

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