Methyl chloroformate → HCID 118389629, compound

HRID 1774603Notes

Reaction equation

HRID 1774603 reaction equation
Br[C:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]3[O:15][CH2:14][CH2:13][CH2:12][C:11]=3[CH:16]=2)=[C:5]([CH:17]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:18]([O:20][CH3:21])=[O:19])[N:4]([CH3:27])[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].CC1(C)OB([C:40]2[CH2:45][CH2:44][CH2:43][C:42](=[O:46])[CH:41]=2)OC1(C)C.C(N(CC)CC)C.ClC(OC)=O>C(COC)OC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.O.C(O)C>[C:23]([O:22][CH:17]([C:5]1[N:4]([CH3:27])[N:3]=[C:2]([C:40]2[CH2:45][CH2:44][CH2:43][C:42](=[O:46])[CH:41]=2)[C:6]=1[C:7]1[CH:8]=[CH:9][C:10]2[O:15][CH2:14][CH2:13][CH2:12][C:11]=2[CH:16]=1)[C:18]([O:20][CH3:21])=[O:19])([CH3:26])([CH3:25])[CH3:24]

Participants

11

Reactant 5

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 574964223-(Tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-2-en-1-oneHCID 90095885HCID 90095885, compound

Product 1

HCID 118389629HCID 118389629, compoundYield 61%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

A solution of methyl 2-[3-bromo-4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-1H-pyrazol-5-yl]-2-(tert-butoxy)acetate (11i) (100 mg, 0.229 mmol), disodium carbonate (73 mg, 0.686 mmol), and 3-(tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-2-en-1-one (43b) (51 mg, 0.229 mmol) in a mixture of dimethoxyethane (0.87 mL), ethanol (0.37 mL) and water (0.25 mL) was bubbled with nitrogen for 5 minutes. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (9.3 mg, 0.011 mmol) was added and the reaction mixture was heated at 140° C. for 2 hours. The solution was concentrated in vacuo. Water (2 mL) was added to the residue and the aqueous layer was washed with diethyl ether (2 mL), acidified with 1M hydrochloric acid until pH 3 and extracted with diethyl ether (2×3 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude was dissolved in dichloromethane (1 mL), cooled to 0° C., and under a nitrogen atmosphere, triethylamine (48 μL, 0.343 mmol) and methyl chloroformate (27 μL, 0.343 mmol) were added. The reaction mixture was stirred at 0° C. for 40 minutes and allowed to reach room temperature. Dichloromethane (2 mL) was added, and the mixture was successively washed with 1N hydrochloric acid (2 mL), a saturated solution of sodium hydrogenocarbonate (2 mL), and brine (2 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 70/30) to provide methyl 2-(tert-butoxy)-2-[4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-3-(3-oxocyclohex-1-en-1-yl)-1H-pyrazol-5-yl]acetate (43c) (63 mg, 0.139 mmol, 61%).

Workup

  1. customwas bubbled with nitrogen for 5 minutes
  2. concentrationThe solution was concentrated in vacuo
  3. additionWater (2 mL) was added to the residue
  4. washthe aqueous layer was washed with diethyl ether (2 mL)
  5. extractionextracted with diethyl ether (2×3 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. dissolutionThe crude was dissolved in dichloromethane (1 mL)
  9. temperaturecooled to 0° C.
  10. customto reach room temperature
  11. washthe mixture was successively washed with 1N hydrochloric acid (2 mL)
  12. dry with materialThe organic layer was dried over sodium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 70/30)

Sources & evidence

ORD record
ord-aba36e4c41064267ade059a4d24035f3
Source dataset
uspto-grants-2016_02
Patent number
US09260395B2

Reaction notes

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