Hydrochloric Acid → 2-Bromo-4-tert-butyl-5-nitro-phenol

(2-Bromo-4-tert-butyl-5-nitro-phenyl)methyl carbonate (72.9 g, 219.5 mmol) was charged to a reactor and DCM (291.6 mL) was added. The yellow reaction solution was cooled using an ice bath. Sodium methoxide (67.04 g, 69.11 mL of 5.4 M, 373.2 mmol) was added portion-wise at 2.2-6.9° C. After complete addition, the reaction was slowly warmed to ambient temperature. When complete, the reaction was cooled to 0° C. and quenched with 1M HCl (373.2 mL, 373.2 mmol). The biphasic mixture was stirred for 20 min and transferred to a seperatory funnel. The organic layer was separated and washed with water (300 mL) followed by brine (300 ml). The organic layer was concentrated and the crude product dried under high vacuum. The product was further purified using Supercritical Fluid Chromatography (SFC) separation on a Berger MultiGram III (Mettler Toledo AutoChem, Newark Del.). The method conditions were 20% methanol at 250 mL/min on a PPU column (30*150) from Princeton Chromatography, 100 bar, 35 C, 220 nm. An injection of 3.5 mL of a 55-70 mg/mL solution was injected. The data was collected using SFC ProNTo software. The purified product received from SFC purification was a methanol solvate. To remove the methanol, an azeotropic distillation was performed. The dark yellow solid, 2-bromo, 4-tertbuyl, 5-nitro phenol methanol solvate, (111.3 g, 0.59.9 mmol) was charged to a 1 L round bottom flask, followed by heptane (500 mL). The slurry is heated to 64° C. to obtain a clear solution. The solvent was distilled under reduced pressure (649 mbar) for 30 minutes and then stripped to dryness. This procedure was repeated three times until no MeOH was detected by 1H-NMR. The product was dried under high vacuum for 16 hours to give the product as a dark yellow semi solid. 1H-NMR (400 MHZ, DMSO-d6) δ 11.2 (bs, OH), 7.69 (s, 1H); 7.03 (s, 1H); 1.30 (s, 9H)

1. temperatureThe yellow reaction solution was cooled
2. additionAfter complete addition
3. temperatureWhen complete, the reaction was cooled to 0° C.
4. customtransferred to a seperatory funnel
5. customThe organic layer was separated
6. washwashed with water (300 mL)
7. concentrationThe organic layer was concentrated
8. dry with materialthe crude product dried under high vacuum
9. customThe product was further purified
10. customSupercritical Fluid Chromatography (SFC) separation on a Berger MultiGram III (Mettler Toledo AutoChem, Newark Del.)
11. customThe data was collected
12. customThe purified product received from SFC purification
13. customTo remove the methanol
14. distillationan azeotropic distillation
15. additionThe dark yellow solid, 2-bromo, 4-tertbuyl, 5-nitro phenol methanol solvate, (111.3 g, 0.59.9 mmol) was charged to a 1 L round bottom flask
16. temperatureThe slurry is heated to 64° C.
17. customto obtain a clear solution
18. distillationThe solvent was distilled under reduced pressure (649 mbar) for 30 minutes
19. customThe product was dried under high vacuum for 16 hours
20. customto give the product as a dark yellow semi solid

ORDレコード

ord-6c4936beae8c4dbfa92d496e16b97b64

出典データセット

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08476442B2