Acetophenone → 1-Phenylethanol, (R)-

Chiral hydrogenation of acetophenone was carried out (generally-used procedures; see formula (6) below). The (S,SS)-ruthenium hydride complex (1.5 mg; 0.00125 mmol) synthesized in Example 2 was weighed and placed in a 100 mL glass autoclave equipped with a stirrer coated with polytetrafluoroethylene, and after depressurizing the interior of the vessel to eliminate air, argon was introduced. Acetophenone (600 mg; 5.0 mmol) (made by Nacalai Tesque, Inc.) and 2-propanol (2.5 mL), both of which had been deaerated by argon bubbling in advance, were then added into the vessel by means of a syringe and under an argon gas flow. The procedure of performing pressure reduction and argon introduction while stirring the solution obtained was then repeated 5 times for deaeration. A hydrogen tank was then connected to the autoclave using a hydrogen introduction tube and the replacement of the air inside the introduction tube with hydrogen at 2 atmospheres was performed 5 times. The pressure inside the autoclave was then adjusted to 5 atmospheres and then hydrogen was released carefully until the pressure dropped to 1 atmosphere. After repeating this procedure 10 times, the hydrogen pressure was adjusted to 8 atmospheres and vigorous stirring at 25° C. was performed for 12 hours. After completion of reaction, the solution obtained was concentrated by depressurization. The crude product was then subject to simple distillation under reduced pressure (1 mmHg) to obtain (R)-1-phenylethanol (582 mg; 4.75 mmol; yield: 95%) at an ee of 99% as a colorless oily substance. Both conversion rate and enantiomeric excess were 99% in accordance with GC analysis: GC (column: Chirasil-DEX CB; inner diameter (df): 0.25 mm; size: 0.32 mm×25 m; made by Chromopack, Inc.; column temperature: 105° C.; injection and detection temperature: 200° C.; helium pressure: 41 kPa; retention time (tR) of (R)-1-phenylethanol: 21.7 minutes (99.56%); tR of (S)-1-phenylethanol: 23.5 minutes (0.43%); tR of acetophenone: 9.5 minutes (0.01%)); 1HNMR (400 MHz, CDCl3)δ1.50 (d, 3, J=6.6 Hz, CH3), 4.90 (dq, 1, J=3.3 and 6.6 Hz, CHOH), 7.21-7.41 (m, 5, aromatics); [α]28D: +51.8° (c: 0.984; CH2Cl2); absolute structure: R; literature value: [α]23D+48.6° (c: 0.9-1.1; CH2Cl2), 96% ee (R).

1. customThe (S,SS)-ruthenium hydride complex (1.5 mg; 0.00125 mmol) synthesized in Example 2
2. customequipped with a stirrer
3. additionwas introduced
4. additionwere then added into the vessel by means of a syringe and under an argon gas flow
5. customobtained
6. additiondropped to 1 atmosphere
7. stirringvigorous stirring at 25° C.
8. customAfter completion of reaction
9. customthe solution obtained
10. concentrationwas concentrated by depressurization
11. distillationThe crude product was then subject to simple distillation under reduced pressure (1 mmHg)

ORD record

ord-c144a4e2dcb846b3975e6007a56129af

Source dataset

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06720439B1