ChemicalBook CAS DataBase List 2-BOC-6-METHOXY-3,4-DIHYDRO-1H-ISOQUINOLINE-1-CARBOXYLIC ACID

2-BOC-6-METHOXY-3,4-DIHYDRO-1H-ISOQUINOLINE-1-CARBOXYLIC ACID synthesis

12synthesis methods

Product Name:2-BOC-6-METHOXY-3,4-DIHYDRO-1H-ISOQUINOLINE-1-CARBOXYLIC ACID
CAS Number:499139-27-4
Molecular formula:C16H21NO5
Molecular Weight:307.34

2-tert-butyl 1-methyl 6-methoxy-3,4-dihydroisoquinoline-1,2(1H)-dicarboxylate

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2-BOC-6-METHOXY-3,4-DIHYDRO-1H-ISOQUINOLINE-1-CARBOXYLIC ACID

499139-27-4
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Yield:-

Reaction Conditions:

with methanol;lithium hydroxide monohydrate in tetrahydrofuran; for 12 h;

Steps:

Sodium hydride (0.098 g, 2.44 mmol) was added to 15A (0.500 g, 1.63 mmol) in DMF (5 mL) at 0 °C. The reaction was allowed to come to rt and stirred for 1 h before again cooling the mixture back to 0 °C. Iodomethane (0.10 mL, 1.63 mmol) was slowly added and the mixture allowed to raise to rt. After 16 h, the reaction mixture was diluted with EtOAc (50 mL) and treated with FLO (50 mL). The FLO layer was separated and extracted once again with EtOAc (50 mL). The combined organic extract was washed with brine, dried over Na₂S0₄, filtered, and concentrated. Purification by silica gel chromatography gave colorless oil. The ester was hydrolyzed by dissolution in THF (10 mL), treatment with lithium hydroxide monohydrate (0.14 g, 3.25 mmol) (3 mL), and the addition of MeOH (1 mL). After 12 h, the mixture was diluted with FLO and organics concentrated. The remaining aqueous layer was made acidic with 10% citric acid and extracted with EtOAc (3 x 30 mL). The combined organic extract was washed with FLO, brine, dried over a2S0₄, filtered, and concentrated. This material and tert-butyl 4-aminobenzoate (0.314 g, 1.63 mmol) in pyridine (10 mL) was treated with POCI₃ (0.15 mL, 1.63 mmol) at -10 °C. After stirring for 2 h, the reaction was quenched with H₂O and extracted with EtOAc. The organic layer was washed with FLO, 1.0 M HCl solution, H₂0, brine, dried over Na₂S0₄, filtered, and concentrated. The residue was treated with 50% TFA/DCM. After 2 h, the reaction was concentrated. Purification by reverse phase HPLC and concentrating in vacuo gave 16A as oil. MS (ESI) m/z: 327.3 (M+H)⁺.

References:

WO2013/55984,2013,A1 Location in patent:Paragraph 00287