反应详情

温度

10 °C

(R)—N′-(1-tert-butyl-but-3-enyl)-hydrazinecarboxylic acid benzyl ester (110 g, 398 mmoles) and 500 mL of methylene chloride were added to a 2 L round bottom flask with a thermometer and magnetic stirrer. A solution of K2CO3 (82.51 g, 597 mmol in 200 mL deionized water) was subsequently added, and the flask was cooled to ca. 10° C. Neat 3,5-dimethyl benzoyl chloride (73.82 g, 437.8 mmol) was then added slowly over a period of 20 min. 1 L methylene chloride was used to rinse residual acid chloride into the flask and to dilute the reaction mixture. The temperature was not allowed to exceed 15° C. during the addition. The reaction was stirred overnight, first in an ice bath and then at room temperature. TLC analysis at ca. 16 hours indicated that the reaction was complete with residual acid chloride; the mixture was stirred for a total of ca. 40 hours. The reaction mixture was poured into a 2 L reparatory funnel. The organic layer was collected and combined with a small CH2Cl2 backwash of the aqueous layer. The organic phase was washed once more with 10% K2CO3, washed with brine, and then dried over solid MgSO4/Na2SO4. The mixture was filtered from salts, and solvent was removed in vacuo to obtain a granular light beige solid. The crude product was suspended and stirred in 300 mL of 2:1 hexanes:ether and filtered on a Büchner funnel to substantially remove residual 3,5-dimethylbenzoyl chloride. The collected solids were washed four times more with a combined total of ca. 1200 mL 2:1 hexanes:ether, thereby providing a white granular solid. The product was collected and allowed to dry in the air to yield 144.55 g (R)—N′-(1-tert-butyl-but-3-enyl)-N′-(3,5-dimethyl-benzoyl)-hydrazinecarboxylic acid benzyl ester, yield=88.9%. A 30 g sample of was dissolved in 205 mL boiling methanol and allowed to crystallize at room temperature. The resultant flocculant material was washed in a Büchner with 50 mL CH3OH to give 22.2 g, mp=146° C., (ee>99.9%). An analytical sample of (R)—N′-(1-tert-butyl-but-3-enyl)-N′-(3,5-dimethyl-benzoyl)-hydrazinecarboxylic acid benzyl ester was obtained by twice-recrystallizing this material from boiling CH3OH followed by Kugelrohr short-path distillation and collection as a solid to give a pure white material: mp=145.5-147° C. Rf=0.12 (10:1 hexanes:ethyl acetate); 1H NMR (400 MHz, CDCl3): δ 7.5-7.2 (m, 9H, φ+NH), 7.2-6.8 (m), 6.4 (S), 6.3 (S), 5.95 (br, 5H, benzylic+C═C), 5.4-4.6 (m, 9H, allylic N—CH, φ-CH3), 3.65 (br), 2.5 (m), 2.35 (S), 2.3 (S), 1.2-0.8 (m, 9H, —C(CH3)3); [α]25589−12.8° (c 2.01, CHCl3).

1. washto rinse residual acid chloride into the flask
2. additionto dilute the reaction mixture
3. additionto exceed 15° C. during the addition
4. customat room temperature
5. waitTLC analysis at ca. 16 hours indicated that the reaction
6. stirringthe mixture was stirred for a total of ca. 40 hours
7. additionThe reaction mixture was poured into a 2 L reparatory funnel
8. customThe organic layer was collected
9. washThe organic phase was washed once more with 10% K2CO3
10. washwashed with brine
11. dry with materialdried over solid MgSO4/Na2SO4
12. filtrationThe mixture was filtered from salts, and solvent
13. customwas removed in vacuo
14. customto obtain a granular light beige solid
15. filtrationether and filtered on a Büchner funnel to substantially remove residual 3,5-dimethylbenzoyl chloride
16. washThe collected solids were washed four times more with a combined total of ca. 1200 mL 2:1 hexanes
17. customether, thereby providing a white granular solid
18. customThe product was collected
19. customto dry in the air