Tetrabutylammonium Fluoride → 7-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 863906Notes

Reaction equation

HRID 863906 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([O:20][Si](C(C)(C)C)(C)C)=[C:13]([O:18][CH3:19])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])[CH3:3].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH3:4][C:2]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([OH:20])=[C:13]([O:18][CH3:19])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:1])[CH3:3]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 190420613,4-dihydro-7-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-6-methoxy-2(1H)-isoquinolinecarboxylic acid-1,1-dimethylethyl ester

Product 1

HCID 534153467-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 6.0 g portion of 3,4-dihydro-7-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-6-methoxy-2(1H)isoquinolinecarboxylic acid-1,1-dimethylethyl ester is dissolved in 30 mL tetrahydrofuran and cooled to 0° C. To this is added 22.8 mL of a 1.0M solution of tetrabutylammonium fluoride, while stirring. The reaction mixture is brought to room temperature, and stirred for three hours. The reaction is quenched with 10 mL saturated sodium bicarbonate solution and 10 mL water, followed by the addition of 20 mL diethyl ether. After separating the layers, the aqueous phase is extracted with 2×20 mL diethyl ether. The combined organic layers are washed with 20 mL brine, and dried over magnesium sulfate. Following removal of the solvent, the product is purified by silica gel chromatography (eluting with 2:1 hexane/ethyl acetate) to produce 4.15 g of the desired product as a white solid. mp 80°-83° C. MS(Hi res): m/z Calcd for C15H21NO4 279.1470 Found 279.1469 Calcd for C15H21NO4 : C=64.50, H=7.58, N=5.01 Found C=64.47, H=7.61, N=5.19

Workup

  1. customis brought to room temperature
  2. stirringstirred for three hours
  3. customThe reaction is quenched with 10 mL saturated sodium bicarbonate solution and 10 mL water
  4. additionfollowed by the addition of 20 mL diethyl ether
  5. customAfter separating the layers
  6. extractionthe aqueous phase is extracted with 2×20 mL diethyl ether
  7. washThe combined organic layers are washed with 20 mL brine
  8. dry with materialdried over magnesium sulfate
  9. customremoval of the solvent
  10. customthe product is purified by silica gel chromatography (eluting with 2:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-457bc60ea7f94ba5abe031c768126927
Source dataset
uspto-grants-1996_10
Patent number
US05561141

Reaction notes

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