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Structure of 170097-67-3

Chemical Structure| 170097-67-3

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Product Details of [ 170097-67-3 ]

CAS No. :170097-67-3
Formula : C15H19NO4
M.W : 277.32
SMILES Code : O=C(C1=CC2=C(CN(C(OC(C)(C)C)=O)CC2)C=C1)O
MDL No. :MFCD05861548
InChI Key :UHOIFEOHBGCPHE-UHFFFAOYSA-N
Pubchem ID :11357887

Safety of [ 170097-67-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 170097-67-3 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 170097-67-3 ]
  • Downstream synthetic route of [ 170097-67-3 ]

[ 170097-67-3 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 170097-67-3 ]
  • [ 622867-52-1 ]
YieldReaction ConditionsOperation in experiment
99.3%
Stage #1: With borane-THF In tetrahydrofuran at 25℃; for 16 h; Inert atmosphere
Stage #2: With sodium carbonate In tetrahydrofuran; water for 0.25 h;
Example 16
Preparation of intermediate 6-bromomethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (D-1)
To a solution of 3,4-dihydro-1H-isoquinoline-2,6-dicarboxylic acid 2-tert-butyl ester (12.50 g, 45.08 mmol) in dry THF (125.0 mL), under nitrogen at 25° C., is added via syringe borane THF complex (99.17 mL, 99.17 mmol) The mixture is stirred at 25° C. for 16 h then water (10.0 mL) is slowly added followed by 2.0 M Na2CO3 (15.0 mL).
This mixture is stirred for 15 min and then is diluted with EtOAc and the organic layers are collected.
The organics are rinsed with 1M HCl, dried over MgSO4, and concentrated under reduced pressure to afford an oil.
The oil is purified by silica gel chromatography to yield D-1-1 (11.8 g, 99.3percent yield), as a white solid.
To a solution of alcohol, D-1-1, (9.50 g, 36.1 mmol) and N,N-diisopropylethylamine (9.43 mL, 54.1 mmol) in dichloromethane (200.0 mL) is added triphenylphosphine dibromide (23.79 g, 54.11 mmol) at 0° C.
The reaction is stirred for 1 h then concentrated under reduced pressure.
The resulting residue is purified by silica gel chromatography to yield D-1 (8.74 g, 74percent yield), as a white solid.
11.78 g
Stage #1: With borane-THF In tetrahydrofuran at 25℃; for 16 h; Inert atmosphere
Stage #2: With water; sodium carbonate In tetrahydrofuran for 0.25 h;
Preparation of intermediate 6-bromomethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (4-19) Compound 4-17 (12.50 g, 45.08 mmol) is dissolved in dry THF (125.0 mL) under nitrogen at 25° C. Borane THF complex (99.17 mL, 99.17 mmol) is added via syringe and the mixture is stirred at 25° C. for 16 h. Water (10.0 mL) is slowly added and then 2.0 M Na2CO3 (15.0 mL). This mixture is stirred for 15 min and then is diluted with EtOAc and the organic layers are collected. The organics are rinsed with 1.0 M HCl, dried over MgSO4, and concentrated in vacuo to afford an oil. The oil is purified by silica gel chromatography using a gradient of 10-80percent EtOAc in heptane to yield the desired product, 4-18 (11.78 g), as a white solid.
2 g With borane-THF In tetrahydrofuran at 20℃; for 3 h; Sealed tube; Inert atmosphere Borane-tetrahydrofuran complex in tetrahydrofuran (1.0 M, 15.87 mL, 15.87 mmol) was added dropwise to a stirred solution of 2-(tert-butoxycarbonyl)-1,2,3,4- tetrahydroisoquinoline-6-carboxylic acid (2.0 g, 7.21 mmol) in tetrahydrofuran (50 mL) at ambient temperature under argon in a sealed flask. After stirring for 3 hours, the mixture was carefully quenched with water and sodium hydrogen carbonate solution was added. The mixture was extracted with ethyl acetate (x2) and the combined extracts were washed with brine, dried (anhydrous Na2SO4) and evaporated to give tert-butyl 6- (hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (2.0 g). LCMS m/z = 207.9 [M+H–isobutylene]+.
References: [1] Patent: US2016/24059, 2016, A1, . Location in patent: Paragraph 0308-0309.
[2] Patent: WO2012/122340, 2012, A1, . Location in patent: Page/Page column 77.
[3] Patent: US2014/73629, 2014, A1, . Location in patent: Paragraph 0100; 0101.
[4] Patent: WO2017/160632, 2017, A1, . Location in patent: Page/Page column 78; 79.
[5] Patent: WO2017/216726, 2017, A1, . Location in patent: Page/Page column 643-644.
 

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