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

HRID 1819283Notes

Reaction equation

HRID 1819283 reaction equation
[O:1]=[C:2]1[CH2:11][CH2:10][CH:9]2[CH:4]([CH2:5][CH:6]([C:16]([OH:18])=[O:17])[N:7]([C:12]([O:14][CH3:15])=[O:13])[CH2:8]2)[CH2:3]1.[CH2:19](N(CC)CC)[CH3:20].BrCC>C(#N)C>[O:1]=[C:2]1[CH2:11][CH2:10][CH:9]2[CH:4]([CH2:5][CH:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:7]([C:12]([O:14][CH3:15])=[O:13])[CH2:8]2)[CH2:3]1

Participants

5

Reactant 3

HCID 6332Ethyl BromideHCID 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 VI, Step A, 6-oxo-2-(Pg)-decahydroisoquinoline-3-carboxylic acid (Pg is as herein defined above) is esterified by reaction with a compound of formula R5-Br (where R5 is as herein defined) to provide the 6-oxo-2-(Pg)-decahydroisoquinoline-3-carboxylate intermediate of compound (2). For example 6-oxo-2-methoxycarbonyl-decahydroisoquinoline-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 6-oxo-2-methoxycarbonyl-decahydroisoquinoline-3-carboxylate, a compound of structure (2). 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 (2).

Workup

  1. temperaturecooled
  2. custompartitioned between 50:50 ethyl acetate/heptane and 1N HCL
  3. customThe organic phase is isolated
  4. washwashed 3 times with water, saturated sodium bicarbonate, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-273046cce0484412bae33dede3c4d6a0
Source dataset
uspto-grants-2009_10
Patent number
US07601738B2

Reaction notes

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