Water → HCID 12108676, compound

HRID 478948Notes

Reaction equation

HRID 478948 reaction equation
[CH2:1](Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][C:26]=1[O:27][CH3:28])[CH2:23][N:22]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C@H:21]([C:36]([OH:38])=[O:37])[CH2:20]2.O>CN(C=O)C.[Na+].[I-]>[CH2:1]([O:38][C:36]([C@@H:21]1[CH2:20][C:19]2[C:24](=[CH:25][C:26]([O:27][CH3:28])=[C:17]([O:16][CH3:15])[CH:18]=2)[CH2:23][N:22]1[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:37])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7503Benzyl ChlorideHCID 11430Potassium CarbonateHCID 12108675HCID 12108675, compound

Product 1

HCID 12108676HCID 12108676, compoundYield 93.8%

Reagents, catalysts & solvents 2

HCID 5238Sodium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

Benzyl chloride (116.4 g, 0.92 mol), powdered K2CO3 solids (87 g, 0.63 mol), NaI (6.0 g, 0.04 mol) and Bu4N+Br− (1.5 g, 0.0046 mol) were added to a solution of crude compound (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-(tert-butyloxycarbonyl)-3-isoquinolinecarboxylic acid (297 g, 0.8357 mol) in DMF (890 mL) at 20-25° C. The reaction mixture was stirred at 40-50° C. for 5 h. The reaction mixture then was cooled to 0-5° C., and water (1.78 L) was added in portions (IT<20° C.). The resulting light yellow suspension was stirred at 5-15° C. The mixture was filtered and washed with water (2×600 mL) and heptane (600 mL). The off-white solids were dried under vacuum at 45° C. to afford crude (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-(tert-butyloxycarbonyl)-3-isoquinolinecarboxylic acid benzyl ester (335 g, 93.8% yield). 1H NMR (DMSO-d6) δ: 1.35, 1.45 (s, 9H, C(CH3)3), 2.93-3.18 (m, 2H, CH2CHCOOH), 3.17 (s, 6H, OCH3), 4.30 (d, J=16.15 Hz) and 4.37 (d, J=16.40 Hz, minor rotamer) (1H, CHHN), 4.45 (d, J=16.15 Hz) and 4.52 (d, J=16.40 Hz, minor rotamer) (1H, CHHN), 4.68 (dd, J=5.4, 4.3 Hz) and 4.90 (dd, J=5.9, 2.2 Hz, minor rotamer) (1H, CHCOOH), 6.74, 6.78, 6.81 (s, PhH).

Workup

  1. temperatureThe reaction mixture then was cooled to 0-5° C.
  2. stirringThe resulting light yellow suspension was stirred at 5-15° C
  3. filtrationThe mixture was filtered
  4. washwashed with water (2×600 mL) and heptane (600 mL)
  5. customThe off-white solids were dried under vacuum at 45° C.

Sources & evidence

ORD record
ord-e00e16dc7d764b1f8b63958092ed6238
Source dataset
uspto-grants-2003_11
Patent number
US06642384B1

Reaction notes

Loading…