2-Methyltetrahydrofuran → N-((1S)-1-(4-(1-(4-((2-methylcyclopropyl)methoxy)phenyl)-piperidin-4-yl)phenyl)ethyl)acetamide

HRID 1470767Notes

Reaction equation

HRID 1470767 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[CH:19]=[CH:18][C:17]([C@@H:20]([NH:22][C:23](=[O:25])[CH3:24])[CH3:21])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:26][CH:27]1[CH2:29][CH:28]1[CH2:30]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC1CCCO1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>>[CH3:26][CH:27]1[CH2:29][CH:28]1[CH2:30][O:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[CH:15]=[CH:16][C:17]([C@@H:20]([NH:22][C:23](=[O:25])[CH3:24])[CH3:21])=[CH:18][CH:19]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 73012-MethyltetrahydrofuranHCID 11776Triphenylphosphine3×HCID 75555Diisopropyl diazene-1,2-dicarboxylate3×HCID 138655(2-Methylcyclopropyl)methanolHCID 67125424(S)-N-{1-(4-[1-(4-Hydroxyphenyl)-piperidin-4-yl]-phenyl}-ethyl)-acetamide2×

Product 1

HCID 67970640N-((1S)-1-(4-(1-(4-((2-methylcyclopropyl)methoxy)phenyl)-piperidin-4-yl)phenyl)ethyl)acetamide

Procedure

50 mg (0.15 mmol) (S)—N-{1-(4-[1-(4-Hydroxyphenyl)-piperidin-4-yl]-phenyl}-ethyl)-acetamide (compound 1.48), 14 mg (0.16 mmol) 2-methylcyclopropanemethanol and 38.8 mg (0.15 mmol) triphenylphosphine are added to 2 mL 2-methyl-tetrahydrofurane at 0° C. 30.5 μl (0.15 mmol) di-iso-propyl azodicarboxylate are added and the mixture is allowed to warm to rt. Stirring is continued over night followed by addition of 0.5 equivalents of triphenylphosphine and 0.5 equivalents of di-iso-propyl azodicarboxylate. Stirring is continued for one day and again additional triphenylphosphine and di-iso-propyl azodicarboxylate are added and stirring is continued for 16 h at 50° C. Then the mixture is filtered and purified using reversed phase HPLC (water/MeOH, 0.1% FA) to yield the desired product.

Workup

  1. waitis continued over night
  2. stirringStirring
  3. stirringstirring
  4. waitis continued for 16 h at 50° C
  5. filtrationThen the mixture is filtered
  6. custompurified

Sources & evidence

ORD record
ord-a9b1195a2a894575b84b9977b7961a82
Source dataset
uspto-grants-2015_04
Patent number
US09006450B2

Reaction notes

Loading…