Diisopropylethylamine → 1-Methylene-3-(SR)-((4-(N-(benzylaminocarbonyl)-N-(prop-1-yl)amino)piperidin-1-yl)methyl)-4-(SR)-phenylcyclopentane

HRID 993209Notes

Reaction equation

HRID 993209 reaction equation
[CH2:1]=[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.Cl.[CH2:16]([NH:23][C:24]([N:26]([CH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)[CH2:27][CH2:28][CH3:29])=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[CH2:1]=[C:2]1[CH2:3][CH:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]([CH2:7][N:33]2[CH2:32][CH2:31][CH:30]([N:26]([C:24]([NH:23][CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[O:25])[CH2:27][CH2:28][CH3:29])[CH2:35][CH2:34]2)[CH2:6]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 186777054-(n-(Benzylaminocarbonyl)-(n-prop-1-yl)amino)piperidine hydrochlorideHCID 22890980(+-)-trans-4-Methylene-2-phenylcyclopentanecarboxaldehyde

Product 1

HCID 701578021-Methylene-3-(SR)-((4-(N-(benzylaminocarbonyl)-N-(prop-1-yl)amino)piperidin-1-yl)methyl)-4-(SR)-phenylcyclopentaneYield 85.9%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (+−)-trans-4-methylene-2-phenylcyclopentanecarboxaldehyde from Step C (880 mg, 4.7 mmol) in 1,2-dichloroethane (50 mL) was added 4-(N-(benzylaminocarbonyl)-(N-prop-1-yl)amino)piperidine hydrochloride (1.62 g, 5.2 mmol) and DIPEA (1.0 mL, 5.7 mmol). After 15 min, sodium triacetoxyborohydride (2.0 g, 9.5 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 60% ethyl acetate in hexanes to give the title product (1.8 g) as the free amine. MS (NH3/ESI): m/z 448 (M +1).

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 60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f673f208e8704ea3a95c1555bc63236b
Source dataset
uspto-grants-2002_10
Patent number
US06472410B1

Reaction notes

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