1-Methylimidazole → HCID 86659290, compound

HRID 2363642Notes

Reaction equation

HRID 2363642 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[N:8]=[C:7]([N:9]2[CH2:13][C@@H:12]3[C@H:14]([OH:17])[CH2:15][CH2:16][C@@H:11]3[CH2:10]2)[CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.CN1C=CN=C1.[Br:33][C:34]1[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1>ClCCl>[Br:33][C:34]1[CH:39]=[CH:38][C:37]([S:40]([O:17][C@H:14]2[C@@H:12]3[C@@H:11]([CH2:10][N:9]([C:7]4[CH:6]=[CH:5][CH:4]=[C:3]([C:2]([F:1])([F:18])[F:19])[N:8]=4)[CH2:13]3)[CH2:16][CH2:15]2)(=[O:42])=[O:41])=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 7396p-Bromobenzenesulfonyl chlorideHCID 8471TriethylamineHCID 54674495HCID 54674495, compound

Product 1

HCID 86659290HCID 86659290, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (3aR,4R,6aS)-2-(6-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-ol (3.2 g, 11.75 mmol) from Step 3 in dichloromethane (15 mL) was added triethylamine (4.10 mL, 29.4 mmol) followed by 1-methylimidazole (0.281 mL, 3.53 mmol). The solution was cooled to 0° C. and 4-bromobenzene-1-sulfonyl chloride (4.50 g, 17.63 mmol) was added. The solution was warmed to room temperature and stirred for 16 hours. The reaction mixture was diluted with dichloromethane (12 mL) and washed with aqueous hydrogen chloride (0.1 N, 10 mL×2) and water (10 mL). The organic phase was dried over sodium sulfate and concentrated. The crude material was purified by silica gel chromatography using 0-60% dichloromethane/hexane as eluent to give (3aR,4R,6aS)-2-(6-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-yl 4-bromobenzenesulfonate: 1H NMR (500 MHz, pyridine-d5) δ ppm 7.99-7.90 (m, 2H), 7.77-7.67 (m, 2H), 7.51 (t, J=7.9, 1H), 6.99 (d, J=7.3, 1H), 6.45 (d, J=8.6, 1H), 5.17 (q, J=6.1, 1H), 3.69 (dd, J=11.4, 4.6, 1H), 3.57-3.47 (m, 1H), 3.37 (dd, J=11.4, 8.9, 1H), 3.23 (dd, J=10.7, 4.5, 1H), 2.90-2.78 (m, 1H), 2.67-2.54 (m, 1H), 2.02-1.88 (m, 1H), 1.80 (dq, J=8.2, 6.0, 1H), 1.70 (dtd, J=13.5, 8.6, 7.0, 1H), 1.51-1.37 (m, 1H); MS (ESI+) m/z 491 (M+H)+.

Workup

  1. temperatureThe solution was warmed to room temperature
  2. washwashed with aqueous hydrogen chloride (0.1 N, 10 mL×2) and water (10 mL)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-d52b57470a17467c98908645c9d5cf39
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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