Ammonium Chloride → tert-Butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-hydroxy-3-(tetrahydrofuran-3-yl)propanoate

HRID 56776

Reaction equation

HRID 56776 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:25]#[N:26])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:10](=[O:24])[CH:9]=2)[CH:7]=1.[O:27]1[CH2:31][CH2:30][CH:29]([CH:32]=[O:33])[CH2:28]1.[Cl-].[NH4+]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:25]#[N:26])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH:32]([OH:33])[CH:29]3[CH2:30][CH2:31][O:27][CH2:28]3)[C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[C:10](=[O:24])[CH:9]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 1575683-Furancarboxaldehyde, tetrahydro-HCID 117622654tert-Butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate

Product 1

HCID 117622815tert-Butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-hydroxy-3-(tetrahydrofuran-3-yl)propanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

At −70° C., 6.94 ml (6.94 mmol, 1.3 eq.) of bis(trimethylsilyl)lithium amide (1M in THF) were added dropwise to a solution of 2.00 g (5.34 mmol) of tert-butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate in 50 ml of tetrahydrofuran, the mixture was stirred at −70° C. for 10 min, a solution of 801 mg (8.00 mmol, 1.5 eq.) of tetrahydrofuran-3-carbaldehyde in 4 ml of tetrahydrofuran was added and the mixture was stirred at −70° C. for 90 min. The reaction mixture was warmed to −20° C., and 25 ml of semisaturated aqueous ammonium chloride solution were added. After phase separation, the aqueous phase was extracted with diethyl ether. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried (sodium sulphate), filtered, concentrated under reduced pressure and dried. The crude product was purified by flash chromatography (KP-SIL, petroleum ether/ethyl acetate 33-75%). Yield: 1.49 g (56% of theory)

Workup

  1. stirringthe mixture was stirred at −70° C. for 90 min
  2. temperatureThe reaction mixture was warmed to −20° C.
  3. customAfter phase separation
  4. extractionthe aqueous phase was extracted with diethyl ether
  5. washThe combined organic phases were washed with saturated aqueous sodium chloride solution
  6. dry with materialdried (sodium sulphate)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customdried
  10. customThe crude product was purified by flash chromatography (KP-SIL, petroleum ether/ethyl acetate 33-75%)

Sources & evidence

ORD record
ord-0cf31789b7f54dc1966a2a6529fe8676
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Linked notes

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