Pyridine → 4-[tert-Butoxycarbonylmethyl-(15-tert-butoxycarbonylpentadecanoyl)amino]benzoic acid

HRID 444983Notes

Reaction equation

HRID 444983 reaction equation
C[O:2][C:3](=[O:34])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:33])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:6][CH:5]=1.N1C=CC=CC=1.[H-].[Na+].Br[CH2:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46]>CN(C=O)C.C(#N)C>[C:48]([O:47][C:45]([CH2:44][N:10]([C:11](=[O:33])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:2])=[O:34])=[CH:5][CH:6]=1)=[O:46])([CH3:51])([CH3:50])[CH3:49]

Participants

7

Reactant 4

HCID 1049PyridineHCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 580794834-(15-tert-Butoxycarbonylpentadecanoylamino)benzoic acid methyl ester

Product 1

HCID 580794684-[tert-Butoxycarbonylmethyl-(15-tert-butoxycarbonylpentadecanoyl)amino]benzoic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

4-(15-tert-Butoxycarbonylpentadecanoylamino)benzoic acid methyl ester (235 mg, 0.495 mmol) was evaporated twice from dry pyridine and once from dry acetonitrile, dissolved in dry DMF (4 mL) under nitrogen. 60% NaH (14 mg, 0.594 mmol) was added and the mixture was stirred for 20 minutes at room temperature under nitrogen. tert-Butyl bromoacetate (0.11 mL, 0.742 mmol) was added and the mixture was stirred for 1 hour, the reaction was quenched with ice and separated between water (50 mL) and diethylether (75 mL). The organic phase was dried (Na2SO4) and solvent remove in vacuo. The crude material was dissolved in ethanol (4 mL). NaOH (5 N, 0.15 mL) was added and the mixture was stirred for 1 hour. pH was adjusted to pH=5 with acetic acid and the mixture was separated between water and ethyl acetate. The organic phase was dried (Na2SO4) and solvent removed in vacuo to give the crude product which was purified on RP-HPLC, C-18 with acetonitrile/water gradient (75-95%) containing 0.1% TFA. To give pure 4-[tert-Butoxycarbonylmethyl-(15-tert-butoxycarbonylpentadecanoyl)amino]benzoic acid) (53 mg, 19%)

Workup

  1. stirringthe mixture was stirred for 1 hour
  2. customthe reaction was quenched with ice
  3. customseparated between water (50 mL) and diethylether (75 mL)
  4. dry with materialThe organic phase was dried (Na2SO4) and solvent
  5. customremove in vacuo
  6. dissolutionThe crude material was dissolved in ethanol (4 mL)
  7. additionNaOH (5 N, 0.15 mL) was added
  8. stirringthe mixture was stirred for 1 hour
  9. customthe mixture was separated between water and ethyl acetate
  10. dry with materialThe organic phase was dried (Na2SO4) and solvent
  11. customremoved in vacuo
  12. customto give the crude product which
  13. customwas purified on RP-HPLC, C-18 with acetonitrile/water gradient (75-95%)
  14. additioncontaining 0.1% TFA

Sources & evidence

ORD record
ord-fac2acc4c67f41d6965de551f40275ab
Source dataset
uspto-grants-2013_07
Patent number
US08476228B2

Reaction notes

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