Formaldehyde → HCID 86610913, compound

HRID 2377040Notes

Reaction equation

HRID 2377040 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.[CH2:36]=O.Cl.[CH3:39][NH:40][CH3:41]>C(O)C>[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[CH2:39][N:40]([CH3:36])[CH3:41])[CH2:17]2)[CH3:14])[CH:4]=[C:3]([C:2]([F:1])([F:34])[F:35])[CH:8]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 10473Dimethylamine, hydrochlorideHCID 11306618HCID 11306618, compound

Product 1

HCID 86610913HCID 86610913, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

In a pressure tube, 50 mg (0.0997 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), 10.5 mg (0.3489 mmol) paraformaldehyde, and 20.3 mg (0.2493 mmol) dimethylamine hydrochloride was dissolved in ethanol (4 mL). The tube was sealed and heated in an oil bath for 3 hr at 90° C. The reaction mixture was cooled to RT, the tube was opened and the solvent removed under vacuum. The residue was partitioned between of 5 mL 1N aq. NaOH and EtOAc (3×5 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and the solvent removed under vacuum to provide a yellow oil. The resulting oil was purified by prep TLC on silica gel eluting with methylene chloride/methanol (9/1). The more polar UV active band was isolated to afford the title compound as a glassy yellow solid. 1H-NMR (CD3OD) rotamers: δ: 1.44 (d, 3H, 6.5 Hz), 2.4-2.90 (m, 10H), 3.4-4.6 (m, 8H), 4.82 (br. s, 1H), 6.97 (t, 2H, 8.5 Hz), 7.23 (br. s, 2H), 7.69 (s, 2H), 7.80 (s, 1H)ppm. MS: 559.1 (MH+) observed.

Workup

  1. customThe tube was sealed
  2. temperatureThe reaction mixture was cooled to RT
  3. customthe solvent removed under vacuum
  4. customThe residue was partitioned between of 5 mL 1N aq. NaOH and EtOAc (3×5 mL)
  5. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customthe solvent removed under vacuum
  8. customto provide a yellow oil
  9. customThe resulting oil was purified by prep TLC on silica gel eluting with methylene chloride/methanol (9/1)
  10. customThe more polar UV active band was isolated

Sources & evidence

ORD record
ord-35156794b2f048af9f0325af3284b587
Source dataset
uspto-grants-2008_12
Patent number
US07468437B2

Reaction notes

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