Hydrochloric Acid → Methyl 6-Fluoro-3,4-dihydro-4-(methoxycarbonyl)-2H-benzopyran-4-butanoate

HRID 2248286Notes

Reaction equation

HRID 2248286 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[CH:6][C:7]2[O:12][CH2:11][CH2:10][CH:9]([C:13]([O:15][CH3:16])=[O:14])[C:8]=2[CH:17]=1.Br[CH2:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23].Cl>CN(C=O)C>[F:3][C:4]1[CH:5]=[CH:6][C:7]2[O:12][CH2:11][CH2:10][C:9]([C:13]([O:15][CH3:16])=[O:14])([CH2:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])[C:8]=2[CH:17]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 107604Methyl 4-bromobutyrateHCID 14986536Methyl 6-fluorochromane-4-carboxylate

Product 1

HCID 19094438Methyl 6-Fluoro-3,4-dihydro-4-(methoxycarbonyl)-2H-benzopyran-4-butanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of 8.81 g (0.183 mol) 50% NaH in 300 ml of DMF was added, dropwise, a solution of 27.5 g (0.131 mol) of methyl 6-fluoro-2,3-dihydro-4H-benzopyran-4-carboxylate in 100 ml of DMF. After stirring at room temperature for 1 hour, a solution of 33 g (0.183 mol) of methyl 4-bromobutyrate in 25 ml of DMF was added. The resultant homogeneous solution was stirred at room temperature for 16 hours and then poured onto ice/H2O and acidified to pH 3.0 with concentrated HCl. The aqueous was extracted twice with CH2Cl2 and the combined extracts were dried (NaSO4) and filtered. The filtrate was evaporated in vacuo to an oil (44 g) which was purified by column chromatography on 2 Kg of silica gel, eluting with CH2Cl2 /Et2O. Yield 12 g (30%), an oil; NMR (CDCl3) (delta) 1.5-2 6(m, 8H, CH2), 3.62 (s, 3H, CH3), 3.66 (s, 3H, CH3), 4.21 (t, 2H, J=6 Hz, CH2), 6.7-7.4 (m, 3H, arom).

Workup

  1. additionwas added
  2. stirringThe resultant homogeneous solution was stirred at room temperature for 16 hours
  3. additionpoured onto ice/H2O
  4. extractionThe aqueous was extracted twice with CH2Cl2
  5. dry with materialthe combined extracts were dried (NaSO4)
  6. filtrationfiltered
  7. customThe filtrate was evaporated in vacuo to an oil (44 g) which
  8. customwas purified by column chromatography on 2 Kg of silica gel
  9. washeluting with CH2Cl2 /Et2O

Sources & evidence

ORD record
ord-b9acd89143304f65a9f55c1f4963c291
Source dataset
uspto-grants-1991_08
Patent number
US05039672

Reaction notes

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