Cesium carbonate → tert-Butyl 2,2-dimethyl-5-((6-((2'-(trifluoromethyl)biphenyl-4-yl)methoxy)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-1,3-dioxan-5-ylcarbamate

HRID 710387Notes

Reaction equation

HRID 710387 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([CH2:12][C:13]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:18][O:17][C:16]([CH3:20])([CH3:19])[O:15][CH2:14]1)[CH2:6][CH2:5]2.Cl[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[C:43]([F:46])([F:45])[F:44])=[CH:33][CH:32]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:19][C:16]1([CH3:20])[O:17][CH2:18][C:13]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])([CH2:12][N:7]2[CH2:6][CH2:5][C:4]3[C:9](=[CH:10][CH:11]=[C:2]([O:1][CH2:30][C:31]4[CH:32]=[CH:33][C:34]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=5[C:43]([F:44])([F:45])[F:46])=[CH:35][CH:36]=4)[CH:3]=3)[CH2:8]2)[CH2:14][O:15]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 667266004'-(Chloromethyl)-2-(trifluoromethyl)biphenylHCID 86661788tert-Butyl 5-((6-hydroxy-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamate

Product 1

HCID 86661789tert-Butyl 2,2-dimethyl-5-((6-((2'-(trifluoromethyl)biphenyl-4-yl)methoxy)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-1,3-dioxan-5-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of the product of Step A (0.105 g; 0.27 mmol), the product of Step B (0.08 g; 0.03 mmol) and Cs2CO3 (0.09 g; 0.27 mmol) in anhydrous DMF (1 ml) was stirred overnight at room temperature and solvent was removed in vacuo. The residue was diluted to 15 ml EtOAc and washed with H2O, brine, dried over anhydrous MgSO4, filtered and filtrate evaporated to dryness under reduced pressure. The residue was purified by FCC (SiO2, hexane/EtOAc 9:1) to give the tilted compound (0.12 g; 71%), as colourless solid. 1H-NMR (CDCl3) 1.4 (s, 3H); 1.43 (s, 9H); 1.46 (s, 3H); 2.84 (s, 4H); 2.94 (s, 2H); 3.7 (s, 2H); 3.82 (d, 2H, J=11.5 Hz); 4.07 (d, 2H, J=11.5 Hz); 4.88 (broad s, 1H); 5.07 (s, 2H); 6.74 (d, 1H, J=2.4 Hz); 6.78 (dd, 1H, J=2.4, 8.4 Hz); 6.91 (d, 1H, J=8.4 Hz); 7.29-7.35 (m, 3H); 7.43-7.48 (m, 3H); 7.55 (tr, 1H, J=7.7 Hz); 7.73 (d, 1H, J=7.7 Hz).

Workup

  1. customsolvent was removed in vacuo
  2. additionThe residue was diluted to 15 ml EtOAc
  3. washwashed with H2O, brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. customfiltrate evaporated to dryness under reduced pressure
  7. customThe residue was purified by FCC (SiO2, hexane/EtOAc 9:1)
  8. customto give the tilted compound (0.12 g; 71%)

Sources & evidence

ORD record
ord-41b4e88f73374ea7bd7e0f5337b6bf40
Source dataset
uspto-grants-2015_11
Patent number
US09181182B2

Reaction notes

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