Triphenylphosphine → (2R)-1-amino-3-[4-(3,4-dichlorophenoxy)piperidin-1-yl)propan-2-ol

HRID 2233375Notes

Reaction equation

[N:1]([CH2:4][C@@H:5]([OH:22])[CH2:6][N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)[CH2:9][CH2:8]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[NH2:1][CH2:4][C@@H:5]([OH:22])[CH2:6][N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)[CH2:9][CH2:8]1

Participants

Conditions

Temperature: 60 °C

Procedure

The resulting oil from Step 2 was dissolved in wet tetrahydrofuran (225 ml) and was treated with triphenylphosphine (53.3 g, 203 mmol). The reaction was heated at 60° C. and stirred for 4 h. The solvent was removed under vacuum, the residue re-dissolved into 2N hydrochloric acid (1000 ml) and the aqueous layer was extracted with ethyl acetate (3 times 700 ml). The aqueous phase was basified with a 2N sodium hydroxide solution and extracted with dichloromethane (3 times 1000 ml). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under vacuum. The crude material was purified by chromatography (8% 7N ammonia in methanol/DCM) to give the title compound as a yellow oil (17 g).

Workup

customThe solvent was removed under vacuum
dissolutionthe residue re-dissolved into 2N hydrochloric acid (1000 ml)
extractionthe aqueous layer was extracted with ethyl acetate (3 times 700 ml)
extractionextracted with dichloromethane (3 times 1000 ml)
washThe combined organic layers were washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated under vacuum
customThe crude material was purified by chromatography (8% 7N ammonia in methanol/DCM)

Sources & evidence

ORD record: ord-cc325a14caea47a3b72c208e9651f338
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07709500B2

Reaction notes

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