3-Bromopropionamide → {4-[4-(2-Carbamoylethylthio)phenyl]butyl}carbamic acid tert-butyl ester

HRID 254385Notes

Reaction equation

Br[CH2:2][CH2:3][C:4]([NH2:6])=[O:5].[C:7]([O:11][C:12](=[O:25])[NH:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([SH:24])=[CH:20][CH:19]=1)([CH3:10])([CH3:9])[CH3:8]>C1COCC1.CN1CCOCC1>[C:7]([O:11][C:12](=[O:25])[NH:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]1[CH:19]=[CH:20][C:21]([S:24][CH2:2][CH2:3][C:4](=[O:5])[NH2:6])=[CH:22][CH:23]=1)([CH3:10])([CH3:8])[CH3:9]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 3-Bromopropionic acid amide (0.075 g, 0.5 mmol) in THF (5 ml) was added to a solution of [4-(4-mercaptophenyl)butyl]carbamic acid tert-butyl ester 560 (0.13 g, 0.46 mmol) dissolved in THF (15 mL) and 4-methylmorpholine (NMM) (0.3 mL). The reaction mixture was stirred at 50° C. for 4 h and then cooled to room temperature. Two more equivalents of 3-bromoprionic acid amide (0.15 g, 1 mmol) were added. The mixture was further stirred at room temperature for 2 days. The solvent was removed under reduced pressure and the residue was purified by flash chromatography (silica gel, chloroform/methanol/ammonium hydroxide, 15:1:0.1, v/v) to afford the desired product {4-[4-(2-carbamoylethylsulfanyl)phenyl]butyl}carbamic acid tert-butyl ester 570 (0.13 g, 80%) as a white powder. 1H NMR (300 MHz, CD3OD) δ 1.42 (s, 9H), 1.48 (m, 2H) 1.60 (m, 2H), 2.46 (m, 2H), 2.58 (t, 2H), 3.09 (t, 2H), 3.13 (m, 2H), 7.14 (d, 2H), 7.29 (d, 2H). m/z (ESI) 353 [C18H28N2O3S+H]+.

Workup

temperaturecooled to room temperature
stirringThe mixture was further stirred at room temperature for 2 days
customThe solvent was removed under reduced pressure
customthe residue was purified by flash chromatography (silica gel, chloroform/methanol/ammonium hydroxide, 15:1:0.1

Sources & evidence

ORD record: ord-0419e4eea17048b4908161daf12f5d89
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07875619B2

Reaction notes

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