Diisopropylethylamine → HCID 58079446, compound

HRID 445004Notes

Reaction equation

HRID 445004 reaction equation
[C:1]([O:5][C:6]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([NH:24][CH2:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([OH:32])=O)=[CH:28][CH:27]=1)=[O:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.[NH2:64][C@H:65]([C:71]([O:73][C:74]([CH3:77])([CH3:76])[CH3:75])=[O:72])[CH2:66][CH2:67][C:68](=[O:70])[OH:69]>C1COCC1.CN1C(=O)CCC1>[C:74]([O:73][C:71](=[O:72])[C@@H:65]([NH:64][C:30](=[O:32])[C:29]1[CH:28]=[CH:27][C:26]([CH2:25][NH:24][C:22](=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[CH:34][CH:33]=1)[CH2:66][CH2:67][C:68]([OH:70])=[O:69])([CH3:77])([CH3:75])[CH3:76]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1175051-(1,1-Dimethylethyl) hydrogen L-glutamateHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 59687910HCID 59687910, compound

Product 1

HCID 58079446HCID 58079446, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-[(15-tert-butoxycarbonylpentadecanoylamino)methyl]benzoic acid (413 mg, 0.868 mmol) was dissolved in THF (5 mL), the solution was cooled with an icebath. DIPEA (0.33 mL, 1.91 mmol) and TSTU (314 mg, 1.04 mmol) were added. The mixture was stirred under nitrogen while cooling was maintained. After 30 minutes the icebath was removed and the mixture was stirred for additional 3 hours at room temperature. The mixture was diluted with NMP (5 mL) and H-GluOtBu (0.21 g, 1.04 mmol) was added, the mixture was stirred overnight at room temperature. The mixture was separated between ethyl acetate (100 mL) and water (100 mL), the organic phase dried (Na2SO4) and solvent removed in vacuo. The crude material was purified on silica using DCM/ethanol (90:10) to give (S)-2-{4-[(15-tert-Butoxycarbonyl-pentadecanoylamino)-methyl]-benzoylamino}-pentanedioic acid 1-tert-butyl ester.

Workup

  1. temperaturethe solution was cooled with an icebath
  2. temperaturewhile cooling
  3. temperaturewas maintained
  4. customAfter 30 minutes the icebath was removed
  5. stirringthe mixture was stirred for additional 3 hours at room temperature
  6. additionwas added
  7. stirringthe mixture was stirred overnight at room temperature
  8. customThe mixture was separated between ethyl acetate (100 mL) and water (100 mL)
  9. dry with materialthe organic phase dried (Na2SO4) and solvent
  10. customremoved in vacuo
  11. customThe crude material was purified on silica

Sources & evidence

ORD record
ord-86b431910d2944ab983c16eef97dc21f
Source dataset
uspto-grants-2013_07
Patent number
US08476228B2

Reaction notes

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