Potassium Carbonate → 1-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-3-fluoro-pyrrolidine

HRID 640967Notes

Reaction equation

Cl.Cl.[F:3][CH:4]1[CH2:8][CH2:7][NH:6][CH2:5]1.Br[CH2:10][CH2:11][CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].C([O-])([O-])=O.[K+].[K+]>C(#N)C.O>[C:17]([Si:14]([CH3:16])([CH3:15])[O:13][CH2:12][CH2:11][CH2:10][N:6]1[CH2:7][CH2:8][CH:4]([F:3])[CH2:5]1)([CH3:20])([CH3:19])[CH3:18]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 3-Fluoro-pyrrolidine dihydrochloride salt (448 mg, 3.584 mmol) in anhydrous acetonitrile (24 mL) was treated with bromopropoxy-tert-butyldimethyl silane (0.83 mL) and then with K2CO3 (2.5 g, 5 equiv.). The reaction mixture was heated to 50° C. and stirred overnight. The reaction mixture was subsequently diluted with water (75 mL) and extracted with a 6:1 mixture of Hexane and diethyl ether (2×100 mL). The organic layer was washed with NaHCO3(aq) (100 mL) and brine (100 mL) then dried over anhydrous K2CO3. Following filtration and concentration of the filtrate in vacuo the crude product was purified by flash silica gel chromatography (MeOH:EtOAc, 1:20). By 1H NMR the resulting clear oil (0.8 g) was the desired 1-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-3-fluoro-pyrrolidine in a 10:1 ratio with the t-butyldimethylsilanol by-product. This residue was carried on without further purification.

Workup

extractionextracted with a 6:1 mixture of Hexane and diethyl ether (2×100 mL)
washThe organic layer was washed with NaHCO3(aq) (100 mL) and brine (100 mL)
dry with materialthen dried over anhydrous K2CO3
filtrationfiltration and concentration of the filtrate in vacuo the crude product
customwas purified by flash silica gel chromatography (MeOH:EtOAc, 1:20)
customThis residue was carried on without further purification

Sources & evidence

ORD record: ord-b141d4638d294d85a0a0a2508f31772e
Source dataset: uspto-grants-2010_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07692005B2

Reaction notes

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