Triethylamine → (4R,9aR)-6-Cyclopropylmethoxymethyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2,7-dicarboxylic acid 2-tert-butyl ester 7-methyl ester

HRID 1272149Notes

Reaction equation

HRID 1272149 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH2:22][O:23][CH2:24][CH:25]2[CH2:27][CH2:26]2)=[C:14](Br)[CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:5][C:6]([C:14]1[CH:13]=[C:12]2[C:17]([N:18]3[C@H:10]([CH2:11]2)[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:20][C@H:19]3[CH3:21])=[N:16][C:15]=1[CH2:22][O:23][CH2:24][CH:25]1[CH2:27][CH2:26]1)=[O:7]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 69357623(4R,9aR)-7-bromo-6-cyclopropylmethoxymethyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

Product 1

HCID 69361749(4R,9aR)-6-Cyclopropylmethoxymethyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2,7-dicarboxylic acid 2-tert-butyl ester 7-methyl esterYield 87%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1.5 g (3.31 mmol) (4R,9aR)-7-bromo-6-cyclopropylmethoxymethyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester, 0.11 g (0.50 mmol) palladium(II) acetate, 0.68 g (1.66 mmol) 1,3-bis(diphenylphosphino)propane and 1.4 mL (1.0 g, 10.0 mmol) triethylamine in 15 mL MeOH was stirred for 48 h at 100° C. under a carbon monoxide atmosphere (50 bar). The reaction mixture was cooled to room temperature, filtered and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over magnesium sulphate, filtered and evaporated. The residue was purified by column chromatography over silica gel (0.030–0.063 mm) with ethyl acetate:n-hexane (1:3) as eluant to give the compound as a yellow oil (87%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. custompartitioned between ethyl acetate and water
  4. washThe organic phase was washed with brine
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography over silica gel (0.030–0.063 mm) with ethyl acetate:n-hexane (1:3) as eluant

Sources & evidence

ORD record
ord-c9b65a6856b04c9ca3716675f9b24db3
Source dataset
uspto-grants-2007_04
Patent number
US07208494B2

Reaction notes

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