Diisopropylethylamine → 3-(SR)-((4-(N-(4-Nitrobenzyloxycarbonyl)-N-(allyl)amino)piperidin-1-yl)methyl)-4-(SR)-phenylcyclopentan-1-one di-hydrochloride salt

HRID 278274Notes

Reaction equation

HRID 278274 reaction equation
[O:1]=[C:2]1[CH2:6][C@@H:5]([CH:7]=O)[C@H:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:3]1.[ClH:15].[N+:16]([C:19]1[CH:38]=[CH:37][C:22]([CH2:23][O:24][C:25]([N:27]([CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH2:28][CH:29]=[CH2:30])=[O:26])=[CH:21][CH:20]=1)([O-:18])=[O:17].CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[ClH:15].[ClH:15].[N+:16]([C:19]1[CH:20]=[CH:21][C:22]([CH2:23][O:24][C:25]([N:27]([CH:31]2[CH2:36][CH2:35][N:34]([CH2:7][CH:5]3[CH:4]([C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)[CH2:3][C:2](=[O:1])[CH2:6]3)[CH2:33][CH2:32]2)[CH2:28][CH:29]=[CH2:30])=[O:26])=[CH:37][CH:38]=1)([O-:18])=[O:17]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 181876754-(N-(4-nitrobenzyloxycarbonyl)(N-allyl)amino)piperidine hydrochlorideHCID 54453591(+)-trans-3-Formyl-4-phenylcyclopentan-1-one

Product 1

HCID 695575683-(SR)-((4-(N-(4-Nitrobenzyloxycarbonyl)-N-(allyl)amino)piperidin-1-yl)methyl)-4-(SR)-phenylcyclopentan-1-one di-hydrochloride saltYield 68.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (+−)-trans-4-oxo-2-phenylcyclopentanecarboxaldehyde from Step D (327 mg, 1.74 mmol) in 1,2-dichloroethane (20 mL) was added 4-(N-(4-nitrobenzyloxycarbonyl)(N-allyl)amino)piperidine hydrochloride (667 mg, 1.9 mmol) and DIPEA (0.36 mL, 2.1 mmol). After 5 min, sodium triacetoxyborohydride (740 mg, 3.5 mmol) was added and the reaction was stirred at rt for 4 h. The reaction was diluted with methylene chloride, quenched with aq. sodium carbonate and extracted 3 times with methylene chloride. The organic layers were each washed with brine, dried over sodium sulfate, combined and concentrated in vacuo. The residue was purified by FC eluting with a gradient of 35 to 75% ethyl acetate in hexanes to give the title product (365 mg) as the free amine. This was taken up in ether and IM hydrogen chloride in ether (0.5 mL) was added to form the di-hydrochloride salt. The volatiles were removed in vacuo to give the title salt.

Workup

  1. customquenched with aq. sodium carbonate
  2. extractionextracted 3 times with methylene chloride
  3. washeach washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by FC
  7. washeluting with a gradient of 35 to 75% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5ebdccc0dd47422cb7b94885635ed91e
Source dataset
uspto-grants-2002_03
Patent number
US06358979B1

Reaction notes

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