Bromine → HCID 87763456, compound

HRID 2377044Notes

Reaction equation

HRID 2377044 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@@H:16]2[C@@H:20]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[CH2:19][N:18]([C:28]3[CH2:32][CH2:31][C:30](=[O:33])[CH:29]=3)[CH2:17]2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Br:36]Br>C(Cl)Cl.O>[F:10][C:9]([F:11])([F:12])[C:7]1[CH:6]=[C:5]([C@H:13]([O:15][C@@H:16]2[C@@H:20]([C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)[CH2:19][N:18]([C:28]3[CH2:32][CH2:31][C:30](=[O:33])[C:29]=3[Br:36])[CH2:17]2)[CH3:14])[CH:4]=[C:3]([C:2]([F:1])([F:34])[F:35])[CH:8]=1

Participants

5

Reactant 2

HCID 24408BromineHCID 11306618HCID 11306618, compound

Product 1

HCID 87763456HCID 87763456, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

In a round bottomed flask, 150 mg (0.299 mmol) 3-[(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-fluorophenyl)pyrrolidin-1-yl]cyclopent-2-en-1-one (Example 3, step F) was dissolved in methylene chloride (5 mL) under nitrogen atmosphere and cooled to 0° C. To this solution was added a solution of 300 mg (1.877 mmol) bromine in methylene chloride (5 mL). The resulting solution was stirred for 0.25 hr at 0° C. then was quenched by the addition of sat. aq. Na2SO3 until a clear solution resulted. The mixture was diluted with 5 mL water then extracted with methylene chloride (3×5 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and the solvent removed under vacuum. The resulting oil was purified by prep TLC on silica gel eluting with methylene chloride/methanol (95/5) to afford the title compound and a small amount of the less polar 2,2-dibromo compound. Monobromide, 1H-NMR (CD3OD): δ: 1.44 (d, 3H), 2.48 (br. s, 2H), 2.87 (m, 2H), 3.43 (m, 1H), 3.66 (m, 1H), 4.0-4.22 (m, 2H), 4.70-4.83 (m, 2H), 6.98 (t, 2H), 7.18 (dd, 2H), 7.70 (s, 2H), 7.83 (s, 1H)ppm. MS: 580.0 and 582 (MH+) observed. Dibromide, 1H-NMR (CD3OD): δ: 1.46 (d, 3H), 2.82 (d, 1H), 3.24 (dd, 1H), 3.38-4.85 (m, 7H), 5.35, 5.36 (2s, 1H), 7.00 (m, 2H), 7.20 (m, 2H), 7.67-7.87 (m, 3H)ppm. MS: 657.9, 659.9 and 661.9 (MH+) observed.

Workup

  1. customthen was quenched by the addition of sat. aq. Na2SO3 until a clear solution
  2. customresulted
  3. extractionthen extracted with methylene chloride (3×5 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customthe solvent removed under vacuum
  7. customThe resulting oil was purified by prep TLC on silica gel eluting with methylene chloride/methanol (95/5)

Sources & evidence

ORD record
ord-6738222cb1b44f10b8aef406b2fe088f
Source dataset
uspto-grants-2008_12
Patent number
US07468437B2

Reaction notes

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