Diisopropylethylamine → (3S*,5R*)-3-[Benzyl-(3-methyl-2-phenyl-butyl)-carbamoyl]-5-tert-butoxycarbonylamino-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester

HRID 1698305Notes

Reaction equation

HRID 1698305 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([N:18]3[CH2:23][C@H:22]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][C@H:20]([C:32]([OH:34])=O)[CH2:19]3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH2:35]([NH:42][CH2:43][CH:44]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[CH:45]([CH3:47])[CH3:46])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(N(C(C)C)C(C)C)C.CCCP(=O)=O>CC(N(C)C)=O>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([N:18]3[CH2:23][C@H:22]([NH:24][C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[CH2:21][C@H:20]([C:32](=[O:34])[N:42]([CH2:35][C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)[CH2:43][CH:44]([C:48]4[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=4)[CH:45]([CH3:47])[CH3:46])[CH2:19]3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 16167369Propylphosphoric anhydrideHCID 57870323HCID 57870323, compoundHCID 67273216Benzyl-(3-methyl-2-phenyl-butyl)-amine

Product 1

HCID 69073351(3S*,5R*)-3-[Benzyl-(3-methyl-2-phenyl-butyl)-carbamoyl]-5-tert-butoxycarbonylamino-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred, ice-cooled mixture of (3S*,5R*)-5-tert-butoxycarbonylamino-piperidine-1,3-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl) ester (466.5 mg, 1 mmol), benzyl-(3-methyl-2-phenyl-butyl)-amine (279 mg, 1.1 mmol) and N-ethyldiisopropylamine (1.37 mL, 8 mmol) in dimethylacetamide (6 mL), propylphosphonic anhydride solution (˜50% in DMF, 0.95 mL, ˜1.5 mmol) is added. The reaction mixture is stirred for 7 h at RT and evaporated in vacuo. The residue is dissolved in ethyl acetate and washed twice with an aqueous 10% K2CO3 solution. The organic layer is dried (Na2SO4) and evaporated in vacuo and the residue is purified by flash chromatography (hexane/ethyl acetate). The combined pure fractions are evaporated to afford the title compound as a white amorphous solid. MS: 702.3 [M+H]+; tR (HPLC, Nucleosil C18; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 8 min, then 100% CH3CN+0.1% TFA for 2 min, flow 1.5 ml/min): 8.87 min.

Workup

  1. temperatureTo a stirred, ice-cooled
  2. additionis added
  3. customevaporated in vacuo
  4. dissolutionThe residue is dissolved in ethyl acetate
  5. washwashed twice with an aqueous 10% K2CO3 solution
  6. dry with materialThe organic layer is dried (Na2SO4)
  7. customevaporated in vacuo
  8. customthe residue is purified by flash chromatography (hexane/ethyl acetate)
  9. customThe combined pure fractions are evaporated

Sources & evidence

ORD record
ord-528c3bdb36124b1ab1b1de0ca496db42
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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