Benzyl chloroformate → HCID 15487827, compound

HRID 1018983Notes

Reaction equation

HRID 1018983 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][C@@H:7]([C:12]([OH:14])=[O:13])[NH:8][CH2:9]2)=[CH:4][CH:3]=1.[C:15](=O)(O)[O-].[Na+].Cl[C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22].C[Si](C=[N+]=[N-])(C)C>CO.C1C=CC=CC=1.CCCCCC.O.O1CCCC1>[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][C@@H:7]([C:12]([O:14][CH3:15])=[O:13])[N:8]([C:21]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])[CH2:9]2)=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 10387Benzyl chloroformateHCID 167693TrimethylsilyldiazomethaneHCID 516892Sodium BicarbonateHCID 2733173L-7-Hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

Product 1

HCID 15487827HCID 15487827, compoundYield 112.5%

Reagents, catalysts & solvents 5

HCID 241BenzeneSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a mixture of (3S)-1,2,3,4-tetrahydro-7-hydroxy-isoquinoline-3-carboxylic acid (1.00 g, 5.18 mmol), sodium bicarbonate(0.88 g, 10.5 mmol), tetrahydrofuran (30 mL), and water (30 mL) was added benzyl chloroformate (0.84 mL, 5.88 mmol) at room temperature. The mixture was stirred overnight and concentrated to about 10 mL. The residue was acidified with 20% HCl until pH ˜4. The white solid formed was filtered and washed with water, and the filtrate was extracted with dichloromethane (×3). The organic layer was dried, concentrated, and combined with the white solid from filtration. To a solution of this compound (1.85 g, 5.66 mmol) in methanol (15 mL) and benzene (10 mL) at 4° C. was added 2.0 M (trimethylsilyl)diazomethane (4.2 mL, 8.4 mmol) in hexane. After 2 hours at 4° C., the solution was concentrated to give the title compound as a yellow oil (1.99 g, 100%). 1H NMR (CDCl3) δ 7.40-7.30 (m, 5H), 6.96 (d, 1H, J=8.1 Hz), 6.67-6.64 (m, 1H), 6.57 (d, 1H, J=14.3 Hz), 5.25-5.11 (m, 3H), 4.68 (d, 1H, J=14.9 Hz), 4.55-4.45 (m, 1H), 3.60 (s, 1.5 14), 3.52 (s, 1.5H), 3.19-3.06 (m, 2H).

Workup

  1. concentrationconcentrated to about 10 mL
  2. customThe white solid formed
  3. filtrationwas filtered
  4. washwashed with water
  5. extractionthe filtrate was extracted with dichloromethane (×3)
  6. customThe organic layer was dried
  7. concentrationconcentrated
  8. filtrationcombined with the white solid from filtration
  9. waitAfter 2 hours at 4° C.
  10. concentrationthe solution was concentrated

Sources & evidence

ORD record
ord-75bc9e4551b644679d05592ebd0479db
Source dataset
uspto-grants-2002_11
Patent number
US06486174B2

Reaction notes

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