Ethyl Bromide → 3-Ethyl 2-Methyl 6-oxooctahydroisoquinoline-2,3(1H)-dicarboxylate

HRID 967094Notes

Reaction equation

HRID 967094 reaction equation
[CH2:1](Br)[CH3:2].[CH3:4][O:5][C:6]([N:8]1[CH:17]([C:18]([OH:20])=[O:19])[CH2:16][CH:15]2[CH:10]([CH2:11][CH2:12][C:13](=[O:21])[CH2:14]2)[CH2:9]1)=[O:7].C(N(CC)CC)C>C(#N)C>[CH2:1]([O:19][C:18]([CH:17]1[CH2:16][CH:15]2[CH:10]([CH2:11][CH2:12][C:13](=[O:21])[CH2:14]2)[CH2:9][N:8]1[C:6]([O:5][CH3:4])=[O:7])=[O:20])[CH3:2]

Participants

5

Reactant 3

HCID 6332Ethyl Bromide2×HCID 8471TriethylamineHCID 156901772-Methoxycarbonyl-6-oxo-1,3,4,4a,5,7,8,8a-octahydroisoquinoline-3-carboxylic acid

Product 1

HCID 148779783-Ethyl 2-Methyl 6-oxooctahydroisoquinoline-2,3(1H)-dicarboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

In Scheme X, Step A, the compound of structure (i) is esterified by reaction with a compound of formula Et-Br (where Et represents an ethyl group) to provide the intermediate of compound (i-b). For example 2-methoxycarbonyl-6-oxodecahydroisoquinoline-3-carboxylic acid is dissolved in acetonitrile and treated with triethylamine and bromoethane. The reaction is heated at 50° C. for about 3 hours, cooled and partitioned between 50:50 ethyl acetate/heptane and 1N HCl. The organic phase is isolated and washed 3 times with water, saturated sodium bicarbonate, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to provide ethyl-2-methoxycarbonyl-6-oxodecahydroisoquinoline-3-carboxylate, the compound of structure (i-b). This crude material may then be purified under standard conditions well known in the art. For example, the crude material is dissolved in 10% ethyl acetate/heptane and applied to a plug of silica gel (10 g in 10% ethyl acetate/heptane). The plug is eluted with, 10% ethyl acetate/heptane, 15% ethyl acetate/heptane, and 25% ethyl acetate/heptane. The eluents are combined and concentrated under vacuum to provide the purified compound of structure (i-b).

Workup

  1. customto provide the intermediate of compound (i-b)
  2. temperaturecooled
  3. custompartitioned between 50:50 ethyl acetate/heptane and 1N HCl
  4. customThe organic phase is isolated
  5. washwashed 3 times with water, saturated sodium bicarbonate, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-66ef3a3de5f34785b6297da92031f53f
Source dataset
uspto-grants-2005_10
Patent number
US06953805B2

Reaction notes

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