N-(9-Fluorenylmethoxycarbonyloxy)succinimide → HCID 89858136, compound

HRID 1755457Notes

Reaction equation

HRID 1755457 reaction equation
[NH2:1][C@@H:2]([CH2:6][CH2:7][NH:8][C:9]1[S:10][C:11]([CH:14]=[O:15])=[CH:12][N:13]=1)[C:3]([OH:5])=[O:4].C(=O)(O)[O-].[Na+].[C:21](=O)([O:37]N1C(=O)CCC1=O)[O:22][CH2:23][CH:24]1[C:36]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:30]2[C:25]1=[CH:26][CH:27]=[CH:28][CH:29]=2>C1COCC1.O>[CH:35]1[C:36]2[CH:24]([CH2:23][O:22][C:21]([NH:1][C@@H:2]([CH2:6][CH2:7][NH:8][C:9]3[S:10][C:11]([CH:14]=[O:15])=[CH:12][N:13]=3)[C:3]([OH:5])=[O:4])=[O:37])[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:31]=2[CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 3

HCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 516892Sodium BicarbonateHCID 86700107HCID 86700107, compound

Product 1

HCID 89858136HCID 89858136, compoundYield 23.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the crude material from Example 50 (6.76 g, 9.86 mmol) in a mixture of THF (74.0 ml) and water (24.7 ml) is added sequentially sodium bicarbonate (4.97 g, 59.2 mmol), and (9H-fluoren-9-yl)methyl 2,5-dioxopyrrolidin-1-yl carbonate (3.33 g, 9.86 mmol) and the reaction is stirred at room temp. for 1.5 h. The solvent is removed in vacuo and the residue is partitioned between water (25 mL) and EtOAc (25 mL). The organic layer is discarded, and the aqueous layer treated with 1N HCl until pH 3 is achieved. The aqueous layer is extracted with CH2Cl2 (3×25 mL), the organic layers are combined, washed with brine, dried over MgSO4, filtered and evaporated to dryness to give 1.03 g (20.8%) of the title compound as a pale orange solid. LC/MS (Condition A): ret. T=3.59 min, (M+H)+ 452.14. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.75 (1 H, br. s.), 9.65 (1 H, s), 8.98 (1 H, br. s.), 8.06 (1 H, s), 7.91 (2 H, d, J=7.53 Hz), 7.68-7.83 (3 H, m), 7.39-7.47 (3 H, m), 7.30-7.39 (3 H, m), 4.19-4.39 (3 H, m), 3.97-4.10 (1 H, m), 3.41 (2 H, d, J=4.52 Hz), 2.10 (1 H, dd, J=13.55, 4.77 Hz), 1.90 (1 H, dd, J=13.55, 9.79 Hz).

Workup

  1. customThe solvent is removed in vacuo
  2. customthe residue is partitioned between water (25 mL) and EtOAc (25 mL)
  3. additionthe aqueous layer treated with 1N HCl until pH 3
  4. extractionThe aqueous layer is extracted with CH2Cl2 (3×25 mL)
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-bd3a4f9725a2491d8974e783825d0139
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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