Dimethylformamide → 1-tert-butyl 3-methyl (2S,3S,5R)-5-hydroxy-2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]piperidine-1,3-dicarboxylate

HRID 535054Notes

Reaction equation

HRID 535054 reaction equation
[OH:1][C@H:2]1[CH2:7][NH:6][C@H:5]([C:8]([OH:10])=O)[C@@H:4]([C:11]([O:13][CH3:14])=[O:12])[CH2:3]1.Cl.[C:16]1([C:22]2[CH2:23][CH2:24][NH:25][CH2:26][CH:27]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN(C)C=O.C(N(CC)C(C)C)(C)C.C(Cl)Cl.[C:72]([O:76][C:77](OC(OC(C)(C)C)=O)=[O:78])([CH3:75])([CH3:74])[CH3:73]>O>[OH:1][C@H:2]1[CH2:7][N:6]([C:77]([O:76][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:78])[C@H:5]([C:8]([N:25]2[CH2:24][CH:23]=[C:22]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:27][CH2:26]2)=[O:10])[C@@H:4]([C:11]([O:13][CH3:14])=[O:12])[CH2:3]1

Participants

9

Reactant 7

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 81531Diisopropylethylamine2×HCID 90495Di-tert-butyl dicarbonateHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27238604-Phenyl-1,2,3,6-tetrahydropyridine hydrochlorideHCID 67305204(2S,3S,5R)-5-hydroxy-3-(methoxycarbonyl)piperidine-2-carboxylic acid

Product 1

HCID 696399861-tert-butyl 3-methyl (2S,3S,5R)-5-hydroxy-2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]piperidine-1,3-dicarboxylateYield 51.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of (2S,3S,5R)-5-hydroxy-3-(methoxycarbonyl)piperidine-2-carboxylic acid (1.851 g, 0.009110 mol), 4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (2.14 g, 0.0109 mol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (4.83 g, 0.0109 mol) in N,N-dimethylformamide (15.0 mL, 0.194 mol) was stirred at rt for 5 min, then treated with N,N-diisopropylethylamine (3.81 mL, 0.0219 mol) at rt for 2 h. The reaction mixture was diluted with methylene chloride (10.0 mL, 0.156 mol). The resultant mixture was then treated with N,N-diisopropylethylamine (3.17 mL, 0.0182 mol), followed by di-tert-butyldicarbonate (3.98 g, 0.0182 mol) at rt overnight. The reaction was diluted with water, extracted with EtOAc. The combined organic layers were washed with brine, dried, and concentrated to dry in vacuo. The residue was applied on silica gel, eluting with 0 to 80% EtOAc in hexane, to give the titled compound (2.10 g, 51.9%). MS (ESI): (M+H-Boc)+=345.1.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. customdried
  4. concentrationconcentrated
  5. customto dry in vacuo
  6. washeluting with 0 to 80% EtOAc in hexane

Sources & evidence

ORD record
ord-927d2cfb43c4442c896f260f5228f6f6
Source dataset
uspto-grants-2014_10
Patent number
US08853243B2

Reaction notes

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