Sodium hydride → HCID 69054924, compound

HRID 2100581Notes

Reaction equation

HRID 2100581 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C:13]2[C:12]([C:14]([F:17])([F:16])[F:15])=[CH:11][CH:10]=[CH:9][C:8]=2[C@H:7]2[CH2:18][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:20][C@@H:6]2[NH:5]1.Br[CH2:29][C:30]([O:32][CH3:33])=[O:31]>C1COCC1>[CH3:33][O:32][C:30](=[O:31])[CH2:29][N:5]1[C@H:6]2[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18][C@@H:7]2[C:8]2[CH:9]=[CH:10][CH:11]=[C:12]([C:14]([F:16])([F:17])[F:15])[C:13]=2[C:4]1=[O:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 69054189HCID 69054189, compound

Product 1

HCID 69054924HCID 69054924, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (17 mg of 60% dispersion in mineral oil, hexane-washed, 0.42 mmol) in 2 mL of THF was added (3aR,9bS)-tert-butyl 5-oxo-6-(trifluoromethyl)-3,3a,4,5-tetrahydro-1H-pyrrolo[3,4-c]isoquinoline-2(9bH)-carboxylate from Example 13, Part A (101 mg, 0.28 mmol) in 2 mL of THF. The resulting mixture was stirred at ambient temperature for 30 min, at which time gas evolution has ceased. Then there was added methyl bromoacetate (0.053 mL, 0.56 mmol) and the resulting mixture was stirred at ambient temperature for 1 h. The reaction was quenched with 10 mL of 1 N HCl and extracted with ethyl acetate. The organics were washed with sat'd aq NaHCO3 and brine, dried (MgSO4), filtered through a pad of silica gel and concentrated in vacuo to afford 120 mg (99%) of the title compound which was sufficiently pure to be used without purification. LRMS (ESI): 429.22 (M+H)+.

Workup

  1. stirringthe resulting mixture was stirred at ambient temperature for 1 h
  2. customThe reaction was quenched with 10 mL of 1 N HCl
  3. extractionextracted with ethyl acetate
  4. washThe organics were washed with sat'd aq NaHCO3 and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered through a pad of silica gel
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1bec9532bfe04e269cf6105a9ee21de7
Source dataset
uspto-grants-2009_08
Patent number
US07572805B2

Reaction notes

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