Diisopropylethylamine → 1-(SR)-((t-Butoxycarbonyl)amino)-3-(SR)-((4-(N-(4-nitrobenzyloxycarbonyl)-N-(allyl)amino)piperidin-1-yl)methyl)-4-(SR)-phenylcyclopentane

HRID 2301765Notes

Reaction equation

HRID 2301765 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:13][CH:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]([CH:20]=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[N+:23]([C:26]1[CH:45]=[CH:44][C:29]([CH2:30][O:31][C:32]([N:34]([CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH2:35][CH:36]=[CH2:37])=[O:33])=[CH:28][CH:27]=1)([O-:25])=[O:24].CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:13][CH:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]([CH2:20][N:41]2[CH2:42][CH2:43][CH:38]([N:34]([C:32]([O:31][CH2:30][C:29]3[CH:28]=[CH:27][C:26]([N+:23]([O-:25])=[O:24])=[CH:45][CH:44]=3)=[O:33])[CH2:35][CH:36]=[CH2:37])[CH2:39][CH2:40]2)[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 18187642(SR)-((t-butoxycarbonyl)amino)-3-(SR)-(formyl)-4-(SR)-phenylcyclopentaneHCID 181876754-(N-(4-nitrobenzyloxycarbonyl)(N-allyl)amino)piperidine hydrochloride

Product 1

HCID 181876031-(SR)-((t-Butoxycarbonyl)amino)-3-(SR)-((4-(N-(4-nitrobenzyloxycarbonyl)-N-(allyl)amino)piperidin-1-yl)methyl)-4-(SR)-phenylcyclopentaneYield 101.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-((SR)-((t-butoxycarbonyl)amino)-3-(SR)-(formyl)-4-(SR)-phenylcyclopentane (from Step G, derived from Higher Rf isomer in Step E) (30 mg, 0.11 mmol) in 1,2-dichloroethane (3 mL) was added 4-(N-(4-nitrobenzyloxycarbonyl)(N-allyl)amino)piperidine hydrochloride (45 mg, 0.126 mmol) and DIPEA (0.022 mL, 0.126 mmol). After 15 min, sodium triacetoxyborohydride (45 mg, 0.22 mmol) was added and the reaction was stirred at RT for 6 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 Prep TLC eluting with 5% methanol in methylene chloride to give the title product (66 mg) as the free amine.

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 Prep TLC
  7. washeluting with 5% methanol in methylene chloride

Sources & evidence

ORD record
ord-342bc66a2a1b4404b06a114fc2f7ff2f
Source dataset
uspto-grants-2002_12
Patent number
US06500844B1

Reaction notes

Loading…