Hydrochloric Acid → HCID 57698768, compound

Pyrrolidine (22.0 mL, 0.255 mol) was added to a suspension of intermediate 14, 2-chloro-4-hydroxybenzaldehyde (30.8 g, 0.196 mol) in dichloromethane (620 mL). The reaction mixture was cooled with an ice bath. Sodium triacetoxyborohydride (65.8 g, 0.295 mol) was added in portions under stirring. The reaction mixture was stirred for 12 h at room temperature. Water (600 mL) and dichloromethane (600 mL) were added. The reaction mixture was acidified with concentrated HCl to pH˜2. The organic layer was separated. The aqueous one was subjected to extraction with EtOAc (2×500 mL), and the extracts were discarded. The aqueous fraction was alkalized with a saturated solution of potassium carbonate to pH 9-10. The product was extracted with CHCl3 (3×500 mL). The organic layer was dried with anhydrous Na2SO4 (50 g). The solvent was evaporated in vacuo. The obtained oil was refluxed in Et2O (400 mL) for 1 h. Then hexane (200 mL) was added, and the mixture was cooled. The formed residue was separated by filtration and dried. 1H NMR spectrum showed the presence of acetic acid (2.3% w/w). The residue was dissolved in a mixture of Et2O (100 mL) and CH2Cl2 (100 mL), and a solution of NaOH (0.4 g) in water (4 mL) was added. The product was extracted form the organic layer. The extract was dried with anhydrous Na2SO4 (50 g), evaporated, and coevaporated with dioxane. The title compound (23.5 g, 0.11 mol, 56%) was obtained as a pale-yellow powder. LC/MS data: 212.0 and 214.0 (M+H)+ (calculated for C22H14ClNO 211.7). 1H NMR data (DMSO-d6): 9.73 (br.s., 1H, OH); 7.24 (d, 1H, J=8.3 Hz, Ar—H); 6.78 (d, 1H, J=2.4 Hz, Ar—H); 6.70 (d.d., 1H, J1=8.3 Hz, J2=2.4 Hz, Ar—H); 3.54 (s, 2H, CH2Ar); 2.40-2.47 (m, 4H); 1.63-1.70 (m, 4H).

1. temperatureThe reaction mixture was cooled with an ice bath
2. stirringThe reaction mixture was stirred for 12 h at room temperature
3. customThe organic layer was separated
4. extractionThe aqueous one was subjected to extraction with EtOAc (2×500 mL)
5. extractionThe product was extracted with CHCl3 (3×500 mL)
6. dry with materialThe organic layer was dried with anhydrous Na2SO4 (50 g)
7. customThe solvent was evaporated in vacuo
8. temperatureThe obtained oil was refluxed in Et2O (400 mL) for 1 h
9. additionThen hexane (200 mL) was added
10. temperaturethe mixture was cooled
11. customThe formed residue was separated by filtration
12. customdried
13. dissolutionThe residue was dissolved in a mixture of Et2O (100 mL) and CH2Cl2 (100 mL)
14. additiona solution of NaOH (0.4 g) in water (4 mL) was added
15. extractionThe product was extracted form the organic layer
16. dry with materialThe extract was dried with anhydrous Na2SO4 (50 g)
17. customevaporated

ORD record

ord-95e27ef754554364a966057f45b51d9b

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07812040B2