4-Toluenesulfonyl chloride → (2-(((Tert-butoxycarbonyl)amino)(tetrahydrofuran-3-yl)methyl)-5-chloropyridin-3-yl)methyl4-methylbenzenesulfonate

HRID 1777836Notes

Reaction equation

HRID 1777836 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:14]1[C:19]([CH2:20][OH:21])=[CH:18][C:17]([Cl:22])=[CH:16][N:15]=1)[CH:9]1[CH2:13][CH2:12][O:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.[C:31]1([CH3:41])[CH:36]=[CH:35][C:34]([S:37]([Cl:40])(=[O:39])=[O:38])=[CH:33][CH:32]=1>C(Cl)Cl>[C:1]([O:5][C:6]([NH:7][CH:8]([CH:9]1[CH2:13][CH2:12][O:11][CH2:10]1)[C:14]1[C:19]([CH2:20][O:21][S:37]([C:34]2[CH:35]=[CH:36][C:31]([CH3:41])=[CH:32][CH:33]=2)(=[O:39])=[O:38])=[CH:18][C:17]([Cl:22])=[CH:16][N:15]=1)=[O:23])([CH3:4])([CH3:2])[CH3:3].[C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:14]1[C:19]([CH2:20][Cl:40])=[CH:18][C:17]([Cl:22])=[CH:16][N:15]=1)[CH:9]1[CH2:13][CH2:12][O:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 118282599Tert-butyl((5-chloro-3-(hydroxymethyl)pyridin-2-yl)(tetrahydrofuran-3-yl)methyl)carbamate

Product 2

HCID 118274933(2-(((Tert-butoxycarbonyl)amino)(tetrahydrofuran-3-yl)methyl)-5-chloropyridin-3-yl)methyl4-methylbenzenesulfonateYield 54%HCID 131734771Tert-butyl((5-chloro-3-(chloromethyl)pyridin-2-yl)(tetrahydrofuran-3-yl)methyl)carbamateYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl((5-chloro-3-(hydroxymethyl)pyridin-2-yl)(tetrahydrofuran-3-yl)methyl)carbamate (600 mg, 1.74 mmol) in anhydrous CH2Cl2 (25 mL) was added Et3N (0.5 mL, 2.62 mmol) and p-toluenesulfonyl chloride (400 mg, 2.1 mmol) at 0° C. The mixture was stirred at rt for 2 h. The mixture was then washed with water (3×20 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure and purified by chromatography column on silica gel (eluting with 10% EtOAc in petroleum ether, gradient to 20%) to afford (2-(((tert-butoxycarbonyl)amino)(tetrahydrofuran-3-yl)methyl)-5-chloropyridin-3-yl)methyl4-methylbenzenesulfonate (470 mg, 54%) as a colorless oil and tert-butyl((5-chloro-3-(chloromethyl)pyridin-2-yl)(tetrahydrofuran-3-yl)methyl)carbamate (200 mg, 32%) as a white solid. LCMS: tR=0.947 min in 5-95AB—1.5 min chromatography (MK RP18e 25-2 mm), MS (ESI) m/z 519.1 [M+Na]+.

Workup

  1. washThe mixture was then washed with water (3×20 mL)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. custompurified by chromatography column on silica gel (eluting with 10% EtOAc in petroleum ether, gradient to 20%)

Sources & evidence

ORD record
ord-1c9924a88ef04db7b6cc5f909582c664
Source dataset
uspto-grants-2016_02
Patent number
US09266886B2

Reaction notes

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