Methyl Ethyl Ketone → 6-(4-tert-Butyl-cyclohexyloxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 2404206Notes

Reaction equation

HRID 2404206 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([OH:18])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[C:25]([CH:29]1[CH2:34][CH2:33][CH:32](OS(C)(=O)=O)[CH2:31][CH2:30]1)([CH3:28])([CH3:27])[CH3:26].CC(=O)CC>CC(O)(C)C>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH:32]3[CH2:33][CH2:34][CH:29]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:30][CH2:31]3)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6569Methyl Ethyl KetoneHCID 10796Cesium carbonateHCID 10060623tert-Butyl 6-hydroxy-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 11128255Methanesulfonic acid 4-tert-butyl-cyclohexyl ester

Product 1

HCID 669267656-(4-tert-Butyl-cyclohexyloxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterYield 58.6%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

A mixture of 6-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1.1 g, 4.4 mmol), cesium carbonate (4.3 g, 13 mmol), and methanesulfonic acid 4-tert-butyl-cyclohexyl ester (2.2 g, 8.8 mmol). in t-BuOH (12 mL) and 2-butanone (6.0 mL) was heated in a sealed vial at 100° C. overnight. The mixture was partitioned between water and ether. The organic phase was washed with water, dried over MgSO4, filtered and concentrated. The residue was purified via a silica gel column eluted with EtOAc in hexanes from 0 to 30% to give white precipitate (1.0 g, yield: 58%). 1H NMR (400 MHz, CDCl3) δ 6.99 (d, 1H), 6.74 (dd, 1H), 6.67 (d, 1H), 4.49 (s, 2H), 4.07 (m, 1H), 3.61 (s, 2H), 2.78 (m, 2H), 2.18 (d, 2H), 1.85 (d, 2H), 1.48 (s, 9H), 1.37 (m, 2H), 1.18-1.00 (m, 3H), 0.87 (s, 9H).

Workup

  1. customThe mixture was partitioned between water and ether
  2. washThe organic phase was washed with water
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified via a silica gel column
  7. washeluted with EtOAc in hexanes from 0 to 30%

Sources & evidence

ORD record
ord-9f37b7c1cc474f5cbc5db0f3e86916f0
Source dataset
uspto-grants-2014_08
Patent number
US08802659B2

Reaction notes

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