Methanol → HCID 86644973, compound

HRID 1944229Notes

Reaction equation

HRID 1944229 reaction equation
C(OC([N:8]1[CH2:17][CH:16]([O:18][CH2:19][CH3:20])[C:15]2[C:10](=[CH:11][C:12]([O:29][CH3:30])=[C:13]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:14]=2)[CH2:9]1)=O)(C)(C)C.CO.C(Cl)(=O)C.C(Cl)Cl>C1COCC1.C(OCC)(=O)C.CO>[CH2:22]([O:21][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][C:12]=1[O:29][CH3:30])[CH2:9][NH:8][CH2:17][CH:16]2[O:18][CH2:19][CH3:20])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 6367Acetyl chlorideHCID 59471526HCID 59471526, compound

Product 1

HCID 86644973HCID 86644973, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

6-Benzyloxy-4-ethoxy-7-methoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (4.7 g, 11.4 mmol) was stirred in THF (50 mL) and methanol (5 mL) and cooled to 0° C. before acetyl chloride (2 mL, 28 mmol) was added drop wise. The solution was stirred at rt for an o/n. After addition of DCM (100 mL) the organic layer was washed with a solution of saturated aqueous NaHCO3, water, brine, dried (MgSO4), filtered and concentrated to afford 3.6 g of crude product. Column chromatography (petroleum ether/ethyl acetate 9/1 to 0/1 then ethyl acetate/methanol 1/0 to 10/1) afford 1.5 g (42%) of 6-Benzyloxy-4-ethoxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline F15 and 6-benzyloxy-7-methoxyisoquinoline F16 (0.7 g, 23%). F15 white powder, m.p. 55-56° C., 1H NMR (270 MHz, CDCl3) δ 1.16 (3H, t, J=6.9 Hz), 2.10 (1H, br), 2.91 (1H, dd, J=13.8 and 2.8 Hz), 3.29 (1H, dd, J=13.8 and 2.5 Hz), 3.37-3.61 (2H, m), 3.84 (3H, s), 3.87-3.95 (2H, m), 4.00-4.06 (1H, m), 5.14 (2H, s), 6.53 (1H, s), 6.78 (1H, s), 7.26-7.44 (5H, m). HRMS (ES) calcd. for C19H24NO3 (MH+), 314.1751 found 314.1744. HPLC: tr=4.16 (95.8%) CH3CN/H2O 90/10.

Workup

  1. additionwas added drop wise
  2. washwas washed with a solution of saturated aqueous NaHCO3, water, brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford 3.6 g of crude product

Sources & evidence

ORD record
ord-c172426eb9cf4b668ab2eb2a3f06d655
Source dataset
uspto-grants-2013_03
Patent number
US08394825B2

Reaction notes

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