Acetyl chloride → HCID 16222233, compound

HRID 1710879Notes

Reaction equation

HRID 1710879 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:31])=[C:6]([CH:30]=1)[CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C@H:15]([C:19]([O:21][CH3:22])=[O:20])[N:14]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:13][CH2:12]2.[C:32](Cl)(=[O:34])[CH3:33]>C(Cl)Cl>[C:32]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:31])=[C:6]([CH:30]=1)[CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C@H:15]([C:19]([O:21][CH3:22])=[O:20])[N:14]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[CH2:13][CH2:12]2)(=[O:34])[CH3:33]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 16222232HCID 16222232, compound

Product 1

HCID 16222233HCID 16222233, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2-tert-butyl 1-methyl 6-(5-amino-2-chlorobenzyloxy)-3,4-dihydroisoquinoline-1,2(1H)-dicarboxylate (15 mg, 0.033 mmol) in CH2Cl2 (1 mL) was added TEA (200 μl, 1.43 mmol) followed by the addition of acetyl chloride (10 μl, 0.05 mmol). The reaction was stirred at room temperature for 2 h. It was concentrated and purified by preparative HPLC (Phenomenex 20×100 mm eluting with 0-100% MeOH/H2O (90% in H2O, 0.1% TFA) gradient over 8 min with flow rate 25 mL/min) to yield (R)-2-tert-butyl 1-methyl 6-(5-acetamido-2-chlorobenzyloxy)-3,4-dihydroisoquinoline-1,2(1H)-dicarboxylate as a colorless oil (2 mg, 13%). HPLC retention time (Method C)=3.86 min. LC/MS (ESI) (M+H)+=489.12. 1H NMR (400 MHz, CDCl3) δ ppm 1.47 (s, 5H), 1.50 (s, 4H), 2.19 (s, 3H), 2.80-2.90 (m, 2H), 3.64-3.83 (m, 5H), 3.88 (s, 1H), 5.10 (s, 2H), 5.38 (s, 0.5H), 5.55 (s, 0.5H), 6.72-6.79 (m, 1H), 6.81-6.89 (m, 1H), 7.31-7.68 (m, 4H).

Workup

  1. concentrationIt was concentrated
  2. custompurified by preparative HPLC (Phenomenex 20×100 mm eluting with 0-100% MeOH/H2O (90% in H2O, 0.1% TFA) gradient over 8 min with flow rate 25 mL/min)

Sources & evidence

ORD record
ord-b22061f2376a487dadbad1cb868642e7
Source dataset
uspto-grants-2010_09
Patent number
US07790745B2

Reaction notes

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