Cesium carbonate → HCID 16222230, compound

HRID 1710877Notes

Reaction equation

HRID 1710877 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([C:12]([O:14][CH3:15])=[O:13])[N:7]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:6][CH2:5]2.Br[CH2:24][C:25]1[C:30]([F:31])=[C:29]([Cl:32])[CH:28]=[CH:27][C:26]=1[F:33].C([O-])([O-])=O.[Cs+].[Cs+]>CC(C)=O>[Cl:32][C:29]1[C:30]([F:31])=[C:25]([C:26]([F:33])=[CH:27][CH:28]=1)[CH2:24][O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([C:12]([O:14][CH3:15])=[O:13])[N:7]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:6][CH2:5]2

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27735502-(Bromomethyl)-4-chloro-1,3-difluorobenzeneHCID 58858237(R)-2-tert-butyl 1-methyl 6-hydroxy-3,4-dihydroisoquinoline-1,2(1H)-dicarboxylate

Product 1

HCID 16222230HCID 16222230, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of (R)-2-tert-butyl 1-methyl 6-hydroxy-3,4-dihydroisoquinoline-1,2(1H)-dicarboxylate (1.1 g, 3.58 mmol) in acetone (10 mL) was added 2-(bromomethyl)-4-chloro-1,3-difluorobenzene (0.95 g, 3.94 mmol) followed by the addition of Cs2CO3 (1.28 g, 3.94 mmol). The reaction was stirred at room temperature for 3.5 h and filtered. The solid was rinsed by CH2Cl2 several times. The combined organic layers and filtrate were concentrated and purified by column chromatography on ISCO (40 g) with 0-30% ethyl acetate in hexanes over 25 minutes to yield (R)-2-tert-butyl 1-methyl 6-(3-chloro-2,6-difluorobenzyloxy)-3,4-dihydroisoquinoline-1,2(1H)-dicarboxylate as a white foam (1.62 g, 97%). HPLC retention time (Method C)=4.18 min. LC/MS (ESI) (M+H−Boc)+=368.1. 1H NMR (400 MHz, CDCl3) δ ppm 1.48 (d, J=9.67 Hz, 9H), 2.71-2.88 (m, 1H), 2.88-3.07 (m, 1H), 3.70 (s, 4H), 3.72-3.85 (m, 2H), 5.10 (s, 2H), 6.78 (s, 1H), 6.86 (dd, J=8.79, 2.64 Hz, 1H), 6.89-6.97 (m, 1H), 7.33-7.46 (m, 2H).

Workup

  1. filtrationfiltered
  2. washThe solid was rinsed by CH2Cl2 several times
  3. concentrationThe combined organic layers and filtrate were concentrated
  4. custompurified by column chromatography on ISCO (40 g) with 0-30% ethyl acetate in hexanes over 25 minutes

Sources & evidence

ORD record
ord-fff37581f633453a8d9903eefb891435
Source dataset
uspto-grants-2010_09
Patent number
US07790745B2

Reaction notes

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