Dimethylformamide → (2S,3S,5S)-N-hydroxy-1-methyl-2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-(pyridin-4-yloxy)piperidine-3-carboxamide

HRID 1726691Notes

Reaction equation

HRID 1726691 reaction equation
O[C@H:2]1[CH2:7][N:6]([C:8](OC(C)(C)C)=[O:9])[C@H:5](C(N2CC=C(C3C=CC=CC=3)CC2)=O)[C@@H:4](C(OC)=O)[CH2:3]1.[OH:33][C@H:34]1[CH2:39][NH:38][C@H:37](C(O)=O)[C@@H:36]([C:43]([O:45]C)=O)[CH2:35]1.Cl.C1([C:54]2[CH2:55][CH2:56][NH:57][CH2:58][CH:59]=2)C=CC=CC=1.F[P-](F)(F)(F)(F)F.[N:67]1([O:76][P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN(C)C=O.C(N(CC)[CH:96]([CH3:98])[CH3:97])(C)C.[CH2:101](Cl)Cl.[C:104](OC(OC(OC(C)(C)C)=O)=O)([CH3:107])(C)[CH3:105]>O>[OH:76][NH:67][C:43]([C@H:36]1[CH2:35][C@H:34]([O:33][C:54]2[CH:59]=[CH:58][N:57]=[CH:56][CH:55]=2)[CH2:39][N:38]([CH3:101])[C@@H:37]1[C:8]([N:6]1[CH2:5][CH:4]=[C:3]([C:97]2[CH:96]=[CH:98][CH:107]=[CH:104][CH:105]=2)[CH2:2][CH2:7]1)=[O:9])=[O:45]

Participants

10

Reactant 8

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

Product 1

HCID 86598248(2S,3S,5S)-N-hydroxy-1-methyl-2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-(pyridin-4-yloxy)piperidine-3-carboxamideYield 51.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Part 1. 1-tert-butyl 3-methyl(2S,3S,5R)-5-hydroxy-2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]piperidine-1,3-dicarboxylate: 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 orgnica 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 orgnica 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-b7a342c075cf4fbab3e61e16175e4684
Source dataset
uspto-grants-2009_02
Patent number
US07491724B2

Reaction notes

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