Hydrochloric Acid → (s)-2-(3,4-Dichlorophenyl)morpholine

HRID 77295Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:14][N:13](C(=O)[C@H](OC)C3C=CC=CC=3)[CH2:12][CH2:11][O:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[Li+].[B-](CC)(CC)CC.Cl.[NH4+].[OH-]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[O:10][CH2:11][CH2:12][NH:13][CH2:14]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

Conditions

Temperature: 0 °C

Procedure

Synthesized according to General Procedure 35. To a stirring solution of (R)-1-((S)-2-(3,4-dichlorophenyl)-morpholino)-2-methoxy-2-phenylethanone (620 mg, 1.63 mmol) and THF (9 mL), under N2, at 0° C., was added a solution of Super-hydride in THF (1.0 M, 10.3 mL, 10.3 mmol) dropwise over 10 minutes. The solution was stirred at 0° C. for 30 minutes. The solution was poured into 1M aqueous HCl solution (20 mL). The solution was then basified with NH4OH and extracted with CH2Cl2 (3×50 mL). Purified via silica gel chromatography using 10% MeOH in CH2Cl2 to obtain the desired morpholine, arbitrarily assigned the (5) configuration, as a clear oil (250 mg, 1.1 mmol, 67% yield). 1H-NMR (400 MHz, CDCl3) δ 7.50-7.49 (m, 2H), 7.19 (dd, J=1.6, 8.3 Hz, 1H), 4.47 (dd, J=2.4, 10.4 Hz, 1H), 4.09 (s, 1H), 4.08 (dd, J=1.9, 12.9 Hz, 1H), 3.82-3.75 (m, 1H), 3.09 (dd, J=2.5, 12.5 Hz, 1H), 2.97 (dd, J=3.1, 10.2 Hz, 2H), 2.72-2.69 (m, 1H). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=232.3; tR=0.65 min.

Workup

customSynthesized
extractionextracted with CH2Cl2 (3×50 mL)
customPurified via silica gel chromatography

Sources & evidence

ORD record: ord-c4d7cad2f89d42129614919e023e48be
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841282B2

Reaction notes

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