反应详情

温度

85 °C

A 12 L, 4 neck flask was equipped with an overhead stirrer, an N2 inlet, a type-J Teflon® covered thermocouple, solid addition funnel, and a reflux condenser. The flask was charged with 2-benzyloxy-N-(6-bromo-I-oxoindan-5-yl)acetamide (2000 g, 5.35 mol), as is weight uncorrected for a purity of about 85-90%) and DMAC (3320 ml). Nitrogen was bubbled through the resulting dark viscous solution for 40 minutes. To this stirring solution was added Pd2(dba)3 (52.4 g, 57.0 mmol) followed by DPPF (58.4 g, 105 mmol). The resulting slurry was then heated to 85° C. and was treated with solid Zn(CN)2 (372 g, 3.18 mol) portion-wise over a period of 2 hours. The reaction was stirred at 85° C. for 3 hours. At that time the reaction was judged to be complete (by LC and TLC) and was then allowed to cool to 20° C. and stir overnight at that temperature under an atmosphere of N2. The following morning the reaction mixture was split into two equal portions. Each half was diluted with 12 L of water resulting in the formation of a yellow precipitate. The yellow solid from each portion was collected by vacuum filtration rinsing with water (12 L) followed by IPA (500 ml). The combined solids were allowed to air dry in a fume hood to afford 1701 g (1225 g, 85% yield-corrected for a product purity of 72% by weight and a starting material purity of 85%) of a yellow powder. This material was used directly in the next step without purification. TLC Analysis: Rf=0.28 (50% EtOAC/hexanes). HPLC 10:90 to 90:10 CH3CN:H2O over 15 min. Hold at 90:10 for 2 min, 0.025% TFA Buffer, 1.5 mL/min, UV at 220 nm, Phenomenex Jupiter C18 column 4.6 mm×250 mm at 29° C.: (11.68 min, 93 A %) 1H NMR (CDCl3, 300 MHz): 2.70-2.76 (m, 2H), 3.16-3.23 (m, 2H), 4.16 (s, 2H), 4.74 (s, 2H), 7.32-7.45 (m, 5H), 7.98 (s, 1H), 8.69 (s, 1H), 9.30 (br, 1H).

1. customA 12 L, 4 neck flask was equipped with an overhead stirrer, an N2 inlet
2. additionthermocouple, solid addition funnel, and a reflux condenser
3. customNitrogen was bubbled through the resulting dark viscous solution for 40 minutes
4. temperatureto cool to 20° C.
5. stirringstir overnight at that temperature under an atmosphere of N2
6. customThe following morning the reaction mixture was split into two equal portions
7. additionEach half was diluted with 12 L of water resulting in the formation of a yellow precipitate
8. filtrationThe yellow solid from each portion was collected by vacuum filtration
9. washrinsing with water (12 L)
10. customto air dry in a fume hood
11. customto afford 1701 g (1225 g, 85% yield-
12. customThis material was used directly in the next step without purification
13. waitHPLC 10:90 to 90:10 CH3CN:H2O over 15 min
14. waitHold at 90:10 for 2 min
15. customat 29° C.
16. custom11.68 min, 93