Diisopropylethylamine → 15-{(3,5-Bis-tert-butoxycarbonylmethoxybenzyl)-[2-(2,5-dioxo-pyrrolidin-1-yloxycarbonyl)ethyl]carbamoyl}pentadecanoic acid 4-methoxy-benzyl ester

HRID 445001Notes

Reaction equation

HRID 445001 reaction equation
[CH3:1][O:2][C:3]1[CH:59]=[CH:58][C:6]([CH2:7][O:8][C:9](=[O:57])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24](=[O:56])[N:25]([CH2:31][C:32]2[CH:37]=[C:36]([O:38][CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH:35]=[C:34]([O:47][CH2:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH:33]=2)[CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[CH:5][CH:4]=1.C(N(C(C)C)CC)(C)C.[B-](F)(F)(F)F.CN(C(O[N:82]1[C:87](=[O:88])[CH2:86][CH2:85][C:83]1=[O:84])=[N+](C)C)C>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][O:8][C:9](=[O:57])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24](=[O:56])[N:25]([CH2:31][C:32]2[CH:33]=[C:34]([O:47][CH2:48][C:49]([O:51][C:52]([CH3:53])([CH3:55])[CH3:54])=[O:50])[CH:35]=[C:36]([O:38][CH2:39][C:40]([O:42][C:43]([CH3:44])([CH3:45])[CH3:46])=[O:41])[CH:37]=2)[CH2:26][CH2:27][C:28]([O:30][N:82]2[C:87](=[O:88])[CH2:86][CH2:85][C:83]2=[O:84])=[O:29])=[CH:58][CH:59]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 5807945315-[(3,5-Bis-tert-butoxycarbonylmethoxybenzyl)-(2-carboxyethyl)carbamoyl]pentadecanoic acid 4-methoxybenzyl ester

Product 1

HCID 5807946315-{(3,5-Bis-tert-butoxycarbonylmethoxybenzyl)-[2-(2,5-dioxo-pyrrolidin-1-yloxycarbonyl)ethyl]carbamoyl}pentadecanoic acid 4-methoxy-benzyl esterYield 76.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

15-[(3,5-Bis-tert-butoxycarbonylmethoxybenzyl)-(2-carboxyethyl)carbamoyl]pentadecanoic acid 4-methoxybenzyl ester (190 mg, 0.23 mmol) was dissolved in THF (5 mL). The mixture was cooled with an ice bath. Diisopropylethylamin (0.047 mL, 0.28 mmol) and O—(N-succinimidyl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (83 mg, 0.28 mmol) was added. The mixture was stirred under nitrogen at 0° C. After 30 minutes the ice cooling was removed and the mixture was stirred for an additional 3 hours. Solvent removed in vacuo. The crude product was dissolved in ethyl acetate (50 mL), washed with aqueous phosphate buffer (pH=5.5) (3×25 mL). The organic phase was dried (Na2SO4), solvent removed in vacuo to yield the title compound (163 mg) which was used in subsequent step.

Workup

  1. temperatureThe mixture was cooled with an ice bath
  2. customAfter 30 minutes the ice cooling was removed
  3. stirringthe mixture was stirred for an additional 3 hours
  4. customSolvent removed in vacuo
  5. dissolutionThe crude product was dissolved in ethyl acetate (50 mL)
  6. washwashed with aqueous phosphate buffer (pH=5.5) (3×25 mL)
  7. dry with materialThe organic phase was dried (Na2SO4), solvent
  8. customremoved in vacuo

Sources & evidence

ORD record
ord-23cef32766244f078b7c02a984eda3c9
Source dataset
uspto-grants-2013_07
Patent number
US08476228B2

Reaction notes

Loading…