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

HRID 2421012Notes

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 oil from Step 2 was dissolved in wet tetrahydrofuran (225 mL) and was treated with triphenylphosphine (53.3 g). The reaction was heated at 60° C. and stirred for 4 h. The solvent was removed under vacuum, the residue redissolved into 2N hydrochloric acid (1 L) and the aqueous layer was extracted with ethyl acetate (3×700 mL). The aqueous phase was basified with aqueous 2 N sodium hydroxide solution and extracted with DCM (3×1 L). 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 redissolved into 2N hydrochloric acid (1 L)
extractionthe aqueous layer was extracted with ethyl acetate (3×700 mL)
extractionextracted with DCM (3×1 L)
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-bd6f2005c6d64a60a5bec0b6a64cb27d
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07956070B2

Reaction notes

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