tert-Butyl 4-oxopiperidine-1-carboxylate → 4-[[4-Chloro-3-[[(tricyclo[3.3.1.13,7]dec-1-ylmethyl)amino]carbonyl]phenyl]methylene]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester

HRID 2298081Notes

Reaction equation

HRID 2298081 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]P(=O)(OC)OC)=[CH:4][C:3]=1[C:15]([NH:17][CH2:18][C:19]12[CH2:28][CH:23]3[CH2:24][CH:25]([CH2:27][CH:21]([CH2:22]3)[CH2:20]1)[CH2:26]2)=[O:16].C([N-]C(C)C)(C)C.[Li+].[C:37]([O:41][C:42]([N:44]1[CH2:49][CH2:48][C:47](=O)[CH2:46][CH2:45]1)=[O:43])([CH3:40])([CH3:39])[CH3:38]>O1CCCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[C:47]2[CH2:48][CH2:49][N:44]([C:42]([O:41][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:43])[CH2:45][CH2:46]2)=[CH:4][C:3]=1[C:15]([NH:17][CH2:18][C:19]12[CH2:20][CH:21]3[CH2:27][CH:25]([CH2:24][CH:23]([CH2:22]3)[CH2:28]1)[CH2:26]2)=[O:16]

Participants

6

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2724682Lithium diisopropylamideHCID 86758648[[4-Chloro-3-[[(tricyclo[3.3.1.13,7]dec-1-ylmethyl)amino]carbonyl]phenyl]-methyl]phosphonic acid, dimethyl ester

Product 1

HCID 867586494-[[4-Chloro-3-[[(tricyclo[3.3.1.13,7]dec-1-ylmethyl)amino]carbonyl]phenyl]methylene]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of the crude [[4-chloro-3-[[(tricyclo[3.3.1.13,7]dec-1-ylmethyl)amino]carbonyl]phenyl]methyl]phosphonic acid, dimethyl ester (2.50 g, Example 50a) in tetrahydrofuran (50 ml) at −78 ° C. was added a solution of lithium diisopropylamide (7.30 ml, 2M in tetrahydrofuran). The reaction was allowed to warm to room temperature and stirred for 15 min. N-t-butoxycarbonylpiperidin-4-one (1.52 g) in tetrahydrofuran (5 ml) was then added and the mixture stirred for 24 h. The reaction was diluted with water and extracted with ethylacetate. The organic layer was washed with brine and dried over magnesium sulfate. The crude material was purified on a silica gel (0 to 5% methanol in dichloromethane) to afford the subtitle compound as a white foam.

Workup

  1. stirringthe mixture stirred for 24 h
  2. extractionextracted with ethylacetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customThe crude material was purified on a silica gel (0 to 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-66cf2d7bacdc416083b812e9dd0a1748
Source dataset
uspto-grants-2002_12
Patent number
US06492355B1

Reaction notes

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