Triethylamine → (3R,4S)-3-[(S)-3-(4-fluorobenzyl)-piperidine-1-carbonyl]-4-[(R)-1-phenyl-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1169253Notes

Reaction equation

HRID 1169253 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([NH:13][C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[C@H:10]([C:22]([OH:24])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(CC)CC)C.[F:65][C:66]1[CH:78]=[CH:77][C:69]([CH2:70][C@@H:71]2[CH2:76][CH2:75][CH2:74][NH:73][CH2:72]2)=[CH:68][CH:67]=1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([NH:13][C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[C@H:10]([C:22]([N:73]2[CH2:74][CH2:75][CH2:76][C@@H:71]([CH2:70][C:69]3[CH:68]=[CH:67][C:66]([F:65])=[CH:78][CH:77]=3)[CH2:72]2)=[O:24])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 12174831(S)-3-(4-Fluorobenzyl)piperidineHCID 69748542(3S,4R)-1-BOC--4-((S)-1-phenylethylamino)pyrrolidine-3-carboxylic acid

Product 1

HCID 69748530(3R,4S)-3-[(S)-3-(4-fluorobenzyl)-piperidine-1-carbonyl]-4-[(R)-1-phenyl-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A cloudy solution of (3R,4S)-4-[(R)-1-phenyl-ethylamino]-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (80 mg, 240 μmol) in methylene chloride (5 mL) was treated with benzotriazol-1-yloxy-tripyrrolidinophosphonium hexafluorophosphate (151 mg, 290 μmol) and triethylamine (77 μL, 550 μmol) and stirred for 5 minutes. A solution of the (S)-3-(4-flourobenzyl)-piperdine prepared above in methylene chloride (5 mL) was added and the mixture was stirred at room temperature. After 18 h , the mixture was washed with water and saturated NaHCO3, dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (50% ethyl acetate/hexanes) to provide the product as a gum (100 mg, 82%). 1H NMR (300 mHz, CD3OD) δ7.32-6.95 (7H), 4.42-4.30 (1H), 3.90-2.48 (14H), 1.80-1.62 (3H), 1.40 (bs, 9H), 1.29 (d, 3H); mass spec. (ES+) m/z 510.4.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature
  3. waitAfter 18 h
  4. washthe mixture was washed with water and saturated NaHCO3
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0d04fb397d4b4165b2a1432b831b05a4
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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