تفاعل #1135091

معادلة التفاعل

2,2-difluoro-benzo[1,3]dioxole-4-carbonyl chloride

2-aminoindan-2-carboxylic acid

DCM

DIPEA

→

dark brown foam

المردود 112.9%

2-[(2,2-Difluoro-benzo[1,3]dioxole-4-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

المردود 112.9%

المذيبات

iPrOH DCM

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONA stirring bar is added
2. 2
   أخرىThe reaction is capped
3. 3
   أخرىis completely consumed
4. 4
   أخرىThe contents of the reaction flask are transferred to a reparatory funnel
5. 5
   workup.ADDITIONdiluted with EtOAc (60 mL)
6. 6
   غسيلThis is washed with dilute aqueous HCl (2×25 mL), saturated aqueous NaHCO3 (2×25 mL), and brine (25 mL)
7. 7
   تجفيفdried over MgSO4
8. 8
   ترشيحfiltered
9. 9
   أخرىevaporated

الإجراء التجريبي

A 100 mL round bottom flask is charged with 2-aminoindan-2-carboxylic acid (340 mg, 1.66 mmol) and dry DCM (6 mL). A stirring bar is added and stirring is initiated. DIPEA (0.46 mL, 2.65 mmol) is added. 2-[(2,2-difluoro-benzo[1,3]dioxole-4-carbonyl chloride (438 mg, 1.99 mmol) is added. 4-Dimethylaminopyridine ([MFCD0006418], 2 mg, cat.) is added. The reaction is capped. After 18 days, tlc analysis (silica, 5% iPrOH/DCM) indicates that the starting is completely consumed. The contents of the reaction flask are transferred to a reparatory funnel and diluted with EtOAc (60 mL). This is washed with dilute aqueous HCl (2×25 mL), saturated aqueous NaHCO3 (2×25 mL), and brine (25 mL), dried over MgSO4, filtered and evaporated by pumping to constant weight to yield 0.73 g of dark brown foam. This is diluted with DCM and applied to a silica column (40 g) on an ISCO Companion. The column is eluted with 3 column volumes of 10% EtOAc-heptanes followed by a linear gradient to 50% EtOAc/heptanes over 10 Column Volumes. And then 90% EtOAc/heptanes for 2 Column Volumes. 17 mL fractions of UV positive eluent are collected. Fraction 8-10 are combined and evaporated by pumping to constant weight to give light orange solid (0.57 g, 88%).

المصدر