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

HRID 2355530Notes

Reaction equation

HRID 2355530 reaction equation
[CH:1]1([C@@H:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:14])[CH2:9][C@H:8]2[NH:23][C:24](OC2C=CC([N+]([O-])=O)=CC=2)=[O:25])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:36][C:37]1[C:38]([F:57])=[C:39]([C@:43]([C@@H:51]2[CH2:56][CH2:55][CH2:54][NH:53][CH2:52]2)([OH:50])[CH2:44][CH2:45][CH2:46][CH2:47][O:48][CH3:49])[CH:40]=[CH:41][CH:42]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:36][C:37]1[C:38]([F:57])=[C:39]([C@:43]([C@@H:51]2[CH2:56][CH2:55][CH2:54][N:53]([C:24]([NH:23][C@H:8]3[C@H:7]([CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]4)[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)=[O:14])[CH2:9]3)=[O:25])[CH2:52]2)([OH:50])[CH2:44][CH2:45][CH2:46][CH2:47][O:48][CH3:49])[CH:40]=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 57544908(3S,4S)-benzyl 4-cyclohexyl-3-((4-nitrophenoxy)carbonylamino)piperidine-1-carboxylateHCID 59382881(S)-1-(3-chloro-2-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol

Product 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-carboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Half of the crude (3S,4S)-benzyl 4-cyclohexyl-3-((4-nitrophenoxy)carbonylamino)piperidine-1-carboxylate from Step 1 was added to a solution of (S)-1-(3-chloro-2-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol (29 mg, 2 equiv) and DIEA (15 μL, 3 equiv) in CH2Cl2 (2 mL). The mixture was stirred for 1 h at rt. LC-MS showed the reaction was complete. The mixture was concentrated and purified by preparative HPLC to afford (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, 63%). LC-MS (3 min) tR=2.40 min., m/z 672 (M+1).

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-2c0d3571f7cf4605aeae54117e1991e9
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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