Isopropyl chloroformate → HCID 58215555, compound

HRID 1661600Notes

Reaction equation

HRID 1661600 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)=[C:6]2[CH3:18].[H-].[Na+].[CH:21]([O:24][C:25](Cl)=[O:26])([CH3:23])[CH3:22]>CN(C=O)C>[CH:21]([O:24][C:25]([N:8]1[C:9]2[C:5](=[CH:4][C:3]([F:2])=[CH:11][CH:10]=2)[C:6]([CH3:18])=[C:7]1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)=[O:26])([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 7917Isopropyl chloroformateHCID 24758Sodium hydrideHCID 44553963HCID 44553963, compound

Product 1

HCID 58215555HCID 58215555, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Fluoro-3-methyl-2-pyridin-3-yl-indole (Example 3, 0.246 g, 1.044 mmol) is dissolved in DMF (9 mL). NaH (60%, 0.054 g, 1.357 mmol) is added and the mixture is stirred for 1 h, whereupon isopropylchloroformate (1.0M in toluene 2.1 mL, 2.1 mmol) is added. The mixture is stirred overnight, quenched with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic phase is dried over MgSO4 and concentrated in vacuo to give a residue, which is purified by silica gel flash chromatography (ethyl acetate-heptane, 1:4 to 2:3) to give 5-fluoro-3-methyl-2-pyridin-3-yl-indole-1-carboxylic acid isopropyl ester as a pale yellow solid. 1H NMR (400 MHz, MeOD) δ ppm 1.07 (d, J=6.3 Hz, 6H), 2.12 (s, 3H), 4.93-5.04 (m, 1H), 7.09-7.17 (m, 1H), 7.30 (dd, J=8.8, 2.3 Hz, 1H), 7.54-7.59 (m, 1H), 7.84-7.89 (m, 1H), 8.23 (dd, J=9.1, 4.5 Hz, 1H), 8.53-8.56 (m, 1H), 8.61 (dd, J=4.5, 1.6 Hz, 1H). HRMS (ESI) m/z 313.1353 [(M+H)+ Calcd for C18H18FN2O2: 313.1352].

Workup

  1. additionis added
  2. customquenched with saturated aqueous sodium bicarbonate
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic phase is dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customto give a residue, which
  7. customis purified by silica gel flash chromatography (ethyl acetate-heptane, 1:4 to 2:3)

Sources & evidence

ORD record
ord-eeac7d67158941eb96c1fcb085b038c2
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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