N-(9-Fluorenylmethoxycarbonyloxy)succinimide → HCID 67185839, compound

HRID 735850Notes

Reaction equation

HRID 735850 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[C:5]([N:7]([CH2:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]([OH:22])=[O:21])=[CH:18][CH:17]=1)[CH2:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)=[O:6])[CH3:2].[C:26](ON1C(=O)CCC1=O)([O:28][CH2:29][CH:30]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]2[C:31]1=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:27].C([O-])(O)=O.[Na+]>O1CCOCC1.O>[CH2:1]([O:3][C:4](=[O:25])[C:5]([N:7]([CH2:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]([OH:22])=[O:21])=[CH:18][CH:17]=1)[CH2:8][CH:9]1[CH2:14][CH2:13][N:12]([C:26]([O:28][CH2:29][CH:30]2[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:36]=3[C:37]3[C:42]2=[CH:41][CH:40]=[CH:39][CH:38]=3)=[O:27])[CH2:11][CH2:10]1)=[O:6])[CH3:2]

Participants

5

Reactant 3

HCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 516892Sodium BicarbonateHCID 67186276HCID 67186276, compound

Product 1

HCID 67185839HCID 67185839, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To a solution of 4-{[[ethoxy(oxo)acetyl](piperidin-4-ylmethyl)amino]methyl}benzoic acid (7.650 g, 16.54 mmol) in dioxane/H2O (1/1) (120 mL) was added Fmoc-OSu (6.697 g, 19.85 mmol) and a 1 M aqueous solution of NaHCO3 (10 mL). The resulting reaction mixture was stirred for 1.25 h, then concentrated under vacuum. The oily residue dissolved in DCM (120 mL) was washed with a 1 N aqueous solution until pH 1, dried over MgSO4, filtered and the solvents were evaporated under vacuum. This crude product was purified by column chromatography over silica gel (AcOEt/c-Hex 1/4 to 1/1 in about 1 h) to give the title compound as a white powder (3.755 g, 40%). 1H NMR (CDCl3, 300 MHz) δ 8.1 (m, 2H), 7.75 (d, 2H, J=7.6 Hz), 7.55 (d, 2H, J=7.2 Hz), 7.38 (m, 4H), 7.29 (t, 2H, J=7.3 Hz), 4.70 (s, 1H), 4.56 (s, 1H), 4.45-4.07 (m, 7H), 3.0 (m, 2H), 2.45 (m, 2H), 1.7-1.5 (m, 1H), 1.40 (m, 2H), 1.38 (t, 1H, J=7.0 Hz), 1.31-1.21 (m, 3H), 1.0-0.8 (m, 2H). M−(LC/MS (ESI)): 569.4; M+(LC/MS (ESI)): 571.8. HPLC (Condition A), Rt: 4.83 min (HPLC purity: 99.3%).

Workup

  1. customThe resulting reaction mixture
  2. concentrationconcentrated under vacuum
  3. dissolutionThe oily residue dissolved in DCM (120 mL)
  4. washwas washed with a 1 N aqueous solution until pH 1
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvents were evaporated under vacuum
  8. customThis crude product was purified by column chromatography over silica gel (AcOEt/c-Hex 1/4 to 1/1 in about 1 h)

Sources & evidence

ORD record
ord-5807ba210ce4492b96d3e56b14568ffc
Source dataset
uspto-grants-2009_09
Patent number
US07592477B2

Reaction notes

Loading…