(3S,4S)-benzyl 3-((R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-4-cyclohexylpiperidine-1-carboxylate → (3R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-((3RS,4RS)-4-cyclohexylpiperidin-3-yl)piperidine-1-carboxamide

HRID 1254414Notes

Reaction equation

HRID 1254414 reaction equation
[Cl:1][C:2]1[C:3]([F:47])=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([NH:24][C@H:25]3[C@H:30]([CH:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)[CH2:29][CH2:28][N:27](C(OCC4C=CC=CC=4)=O)[CH2:26]3)=[O:23])[CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1>[Pd](Cl)Cl.CCOC(C)=O>[Cl:1][C:2]1[C:3]([F:47])=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([NH:24][CH:25]3[CH:30]([CH:31]4[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]4)[CH2:29][CH2:28][NH:27][CH2:26]3)=[O:23])[CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 57544913(3S,4S)-benzyl 3-((R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-4-cyclohexylpiperidine-1-carboxylate

Product 1

HCID 67189164(3R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-((3RS,4RS)-4-cyclohexylpiperidin-3-yl)piperidine-1-carboxamideYield 114.2%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

(3S,4S)-benzyl 3-((R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-4-cyclohexylpiperidine-1-carboxylate (18.4 mg, 0.027 mmol) and palladium(II) chloride (catalytic amount, c.a. 4 mg) were mixed with EtOAc (3 mL). The flask was evacuated and filled by H2 gas (3×). A balloon filled with H2 gas was attached to the flask to maintain the H2 gas atmosphere for 2 h. LC-MS showed most of the starting material had been converted to product. The mixture was concentrated, redissolved in acetonitrile (3 mL), filtered and purified by preparative HPLC to afford (3R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-((3RS,4RS)-4-cyclohexylpiperidin-3-yl)piperidine-1-carboxamide (16.6 mg, quant). LC-MS (3 min) tR=1.58 min., m/z 538 (M+1).

Workup

  1. customThe flask was evacuated
  2. additionfilled by H2 gas (3×)
  3. additionA balloon filled with H2 gas
  4. temperatureto maintain the H2 gas atmosphere for 2 h
  5. concentrationThe mixture was concentrated
  6. dissolutionredissolved in acetonitrile (3 mL)
  7. filtrationfiltered
  8. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-524dc428da68496182afc7e0f41bd32a
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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