Ammonia → 7-[(R)-2-((E)-3-Hydroxy-4-phenyl-but-1-enyl)-6-oxo-piperidin-1-yl]-heptanoic acid amide

HRID 2052932Notes

Reaction equation

C([N:3](CC)CC)C.[OH:8][CH:9]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)/[CH:10]=[CH:11]/[C@H:12]1[CH2:17][CH2:16][CH2:15][C:14](=[O:18])[N:13]1[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25](O)=[O:26].ClC(OCC)=O.N>C(Cl)Cl.CCOC(C)=O>[OH:8][CH:9]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)/[CH:10]=[CH:11]/[C@H:12]1[CH2:17][CH2:16][CH2:15][C:14](=[O:18])[N:13]1[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([NH2:3])=[O:26]

Participants

Conditions

Temperature: 0 °C

Procedure

Triethylamine (9 μL, 0.065 mmol) was added to a solution of 7-[(R)-2-((E)-3-hydroxy-4-phenyl-but-1-enyl)-6-oxo-piperidin-1-yl]-heptanoic acid (11.3 mg, 0.030 mmol) in CH2Cl2 (0.3 mL) at rt. After cooling to 0° C., ethyl chloroformate (3.2 μL, 0.033 mmol) was added. After 1 h at 0° C., a solution of ammonia (0.5 M in 1,4-dioxane, 0.3 mL, 0.15 mmol) was added and the reaction mixture was allowed to warm to rt. After 18 h at rt, the reaction mixture was diluted with EtOAc (10 mL) and washed with aqueous HCl (0.5 M, 3 mL), saturated aqueous NaHCO3 (5 mL) and brine (5 mL) then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→3% MeOH/CH2Cl2, gradient) afforded 3.5 mg (31%) of the title compound.

Workup

temperatureto warm to rt
waitAfter 18 h at rt
washwashed with aqueous HCl (0.5 M, 3 mL), saturated aqueous NaHCO3 (5 mL) and brine (5 mL)
dry with materialthen dried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→3% MeOH/CH2Cl2, gradient)

Sources & evidence

ORD record: ord-843c697f1dab4f02a10b2eac09d018c1
Source dataset: uspto-grants-2008_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07326716B2

Reaction notes

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