Tetrahydrofuran → rac-2-methoxy-2-methyl-propionic acid (1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl ester

HRID 220304Notes

Reaction equation

HRID 220304 reaction equation
[CH3:1][O:2][C:3]1[C:11]2[N:10]=[C:9]([CH2:12][CH2:13][CH2:14][N:15]([CH3:33])[CH2:16][CH2:17][C:18]3([OH:32])[CH2:23][CH:22]4[CH2:24][CH2:25][CH:19]3[CH:20]=[C:21]4[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.CCN(CC)CC.[CH3:41][O:42][C:43]([CH3:48])([CH3:47])[C:44](Cl)=[O:45].C1COCC1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]1[C:11]2[N:10]=[C:9]([CH2:12][CH2:13][CH2:14][N:15]([CH3:33])[CH2:16][CH2:17][C@:18]3([O:32][C:44](=[O:45])[C:43]([O:42][CH3:41])([CH3:48])[CH3:47])[CH2:23][C@H:22]4[CH2:24][CH2:25][C@@H:19]3[CH:20]=[C:21]4[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 221571682-Methoxy-2-methylpropanoyl chlorideHCID 68412969rac-(1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol

Product 1

HCID 90902148rac-2-methoxy-2-methyl-propionic acid (1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 295 mg of rac-(1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol in 6.6 mL of DCM was added 1.4 mL of NEt3, 81 mg of DMAP and 0.8 mL of 2-methoxy-2-methyl propanoyl chloride (prepared as in JOC, 1976, 41, 19, 3182-3187) at 0° C. The reaction mixture was allowed to warm up to rt and stirred for 5 min at rt before 0.3 mL of anh. THF was added. The reaction mixture was stirred overnight at 50° C., extracted with DCM and washed with sat. NaHCO3. The organic phase was dried over anh. Na2SO4 and concentrated in vacuo. The crude product was purified by CC using DCM/MeOH/DIPEA 95/5/1 to yield 214 mg of rac-2-methoxy-2-methyl-propionic acid (1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl ester as white foam.

Workup

  1. additionwas added
  2. extractionextracted with DCM
  3. washwashed with sat. NaHCO3
  4. dry with materialThe organic phase was dried over anh. Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by CC

Sources & evidence

ORD record
ord-d943c51312f64f8db5dcae627a1511bf
Source dataset
uspto-grants-2012_06
Patent number
US08202885B2

Reaction notes

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