Di-tert-butyl Iminodicarboxylate → Methyl 2-((3R,5R,6S)-1-((S)-1-(bis(tert-butoxycarbonyl)amino)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetate

HRID 932136Notes

Reaction equation

HRID 932136 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:24][CH3:25])[CH2:22]O)[C:11](=[O:26])[C@:10]([CH2:28][C:29]([O:31][CH3:32])=[O:30])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C(P(CCCC)(CCCC)=CC#N)CCC.[CH3:49][C:50]([O:53][C:54]([NH:56][C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])=[O:55])([CH3:52])[CH3:51]>C1(C)C=CC=CC=1>[C:60]([O:59][C:57]([N:56]([C:54]([O:53][C:50]([CH3:52])([CH3:51])[CH3:49])=[O:55])[CH2:22][C@@H:21]([N:12]1[C@H:13]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[C@@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[CH2:9][C@@:10]([CH2:28][C:29]([O:31][CH3:32])=[O:30])([CH3:27])[C:11]1=[O:26])[CH2:24][CH3:25])=[O:58])([CH3:63])([CH3:62])[CH3:61]

Participants

5

Reactant 3

HCID 279800Di-tert-butyl IminodicarboxylateHCID 4622928CyanomethylenetributylphosphoraneHCID 58573771Methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetate

Product 1

HCID 67999215Methyl 2-((3R,5R,6S)-1-((S)-1-(bis(tert-butoxycarbonyl)amino)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetate (282 mg, 0.589 mmol; Example 186, Step A), 2-(tributylphosphoranylidene)acetonitrile (171 mg, 0.707 mmol) and di-tert-butyl iminodicarbonate (256 mg, 1.179 mmol) in toluene (3 mL) under argon was stirred at 110° C. for 2 h. Flash column purification on silica gel (0 to 60% EtOAc in hexanes) gave the title compound.

Workup

  1. customFlash column purification on silica gel (0 to 60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-387a643292b04479babfd182a516b7ae
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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