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

HRID 640967ノート

反応式

HRID 640967 の反応式
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]

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 607486(3-Bromopropoxy)(tert-butyl)dimethylsilaneHCID 687005333-Fluoro-pyrrolidine dihydrochloride salt

生成物 1

HCID 686994781-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-3-fluoro-pyrrolidine

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
50 °C

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-b141d4638d294d85a0a0a2508f31772e
出典データセット
uspto-grants-2010_04
特許番号
US07692005B2

反応ノート

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