Isopropylamine → HCID 59837462, compound

HRID 272848Notes

Reaction equation

HRID 272848 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)[CH3:3].Cl[CH2:19][CH2:20][CH2:21]Br.C([O-])([O-])=O.[K+].[K+].[CH:29]([NH2:32])([CH3:31])[CH3:30]>CN(C=O)C>[CH3:3][N:2]([CH2:4][C:5]1([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:19][CH2:20][CH2:21][NH:32][CH:29]([CH3:31])[CH3:30])=[CH:13][CH:12]=2)[CH2:6][CH2:7][O:8][CH2:9][CH2:10]1)[CH3:1]

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 230916214-(4-Dimethylaminomethyl-tetrahydro-pyran-4-yl)-phenol

Product 1

HCID 59837462HCID 59837462, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-Dimethylaminomethyl-tetrahydro-pyran-4-yl)-phenol (730 mg, 3.10 mmol), 3-chloro-1-bromopropane (980 mg, 6.20 mmol), DMF (10 ml) and K2CO3 (1.72 g, 12.40 mmol) were reacted together according to general procedure B. Purification by chromatography on silica, eluant DCM:MeOH (20:1) provided a mixture of bromo and chloro phenoxy ether (250 mg) which was used in the next stage. The mixture (250 mg) was refluxed with isopropyl amine (34° C.) (10 ml, 40 vol) for 7 days. The reaction was concentrated in vacuo and partitioned between 2M NaOH (10 ml) and DCM (10 ml). The aqueous phase was extracted with DCM (3×10 mL). The combined DCM layers were dried over MgSO4, filtered, washed with DCM and concentrated in vacuo. Purification by chromatography on silica, eluant DCM:MeOH:NH3 (95:5:0) increasing gradually to DCM:MeOH:NH3 (90:9:1) gave the title compound as a pale yellow solid (180 mg, 17% over the 2 steps). 1H NMR (400 MHz, CDCl3) δ7.20 (d, 2H), 6.88 (d, 2H), 4.03 (t, 2H), 3.75 (dt, 2H), 3.59-3.50 (m, 2H), 2.89-2.76 (m, 3H), 2.40 (s, 2H), 2.15-2.05 (m, 2H), 2.03-1.93 (m, 2H), 1.96 (s, 6H), 1.88 (ddd, 2H), 1.49 (br s, 1H), 1.07 (d, 6H).

Workup

  1. customPurification by chromatography on silica, eluant DCM:MeOH (20:1)
  2. customprovided
  3. concentrationThe reaction was concentrated in vacuo
  4. custompartitioned between 2M NaOH (10 ml) and DCM (10 ml)
  5. extractionThe aqueous phase was extracted with DCM (3×10 mL)
  6. dry with materialThe combined DCM layers were dried over MgSO4
  7. filtrationfiltered
  8. washwashed with DCM
  9. concentrationconcentrated in vacuo
  10. customPurification by chromatography on silica, eluant DCM:MeOH:NH3 (95:5:0)
  11. temperatureincreasing gradually to DCM:MeOH:NH3 (90:9:1)

Sources & evidence

ORD record
ord-394e5883f37c4483800b9dff51d0368e
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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