Tetrahydrofuran → 1-tert-butyl 3-methyl (2S,3S,5S)-5-[(5-chloropyridin-3-yl)oxy]-2-[4-(4-cyano-3,5-dimethylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonylpiperidine-1,3-dicarboxylate

HRID 535112Notes

Reaction equation

HRID 535112 reaction equation
[C:1]([C:3]1[C:8]([CH3:9])=[CH:7][C:6]([C:10]2[CH2:11][CH2:12][N:13]([C:16]([C@@H:18]3[C@@H:23]([C:24]([O:26][CH3:27])=[O:25])[CH2:22][C@@H:21]([OH:28])[CH2:20][N:19]3[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:17])[CH2:14][CH:15]=2)=[CH:5][C:4]=1[CH3:36])#[N:2].O1CCCC1.[Cl:42][C:43]1[CH:44]=[C:45](O)[CH:46]=[N:47][CH:48]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>>[Cl:42][C:43]1[CH:44]=[C:45]([O:28][C@@H:21]2[CH2:20][N:19]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[C@H:18]([C:16]([N:13]3[CH2:12][CH:11]=[C:10]([C:6]4[CH:7]=[C:8]([CH3:9])[C:3]([C:1]#[N:2])=[C:4]([CH3:36])[CH:5]=4)[CH2:15][CH2:14]3)=[O:17])[C@@H:23]([C:24]([O:26][CH3:27])=[O:25])[CH2:22]2)[CH:46]=[N:47][CH:48]=1

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 5823053-Hydroxy-5-chloropyridineHCID 866214961-tert-butyl 3-methyl (2S,3S,5R)-2-[4-(4-cyano-3,5-dimethylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl-5-hydroxypiperidine-1,3-dicarboxylate

Product 1

HCID 866214951-tert-butyl 3-methyl (2S,3S,5S)-5-[(5-chloropyridin-3-yl)oxy]-2-[4-(4-cyano-3,5-dimethylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonylpiperidine-1,3-dicarboxylateYield 36.9%

Conditions

Temperature
70 °C

Procedure

To a solution of 1-tert-butyl 3-methyl (2S,3S,5R)-2-[4-(4-cyano-3,5-dimethylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl-5-hydroxypiperidine-1,3-dicarboxylate (100 mg, 0.0002 mol) in tetrahydrofuran (0.912 mL, 0.0112 mol) was added 5-chloropyridin-3-ol (35.0 mg, 0.000270 mol), triphenylphosphine (70.8 mg, 0.000270 mol), followed by diisopropyl azodicarboxylate (0.0532 mL, 0.000270 mol). The mixture was heated at 70 Celsius overnight. After concentrated to dry, the mixture was purified on silica gel, elutin with 0 to 40% EtOAc in hexane, to yield the desired product (45 mg, 32.84%). MS (ESI) (M+H) 609.1.

Workup

  1. concentrationAfter concentrated
  2. customto dry
  3. customthe mixture was purified on silica gel, elutin with 0 to 40% EtOAc in hexane

Sources & evidence

ORD record
ord-83ba96b2ad7f470bb08c1fac6596d8cf
Source dataset
uspto-grants-2014_10
Patent number
US08853243B2

Reaction notes

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