Carbon Dioxide → HCID 66738888, compound

HRID 1473005Notes

Reaction equation

HRID 1473005 reaction equation
[CH:1]([N:4]([CH2:8][CH2:9][C@@H:10]([C:17]1[CH:22]=[C:21](Br)[CH:20]=[CH:19][C:18]=1[O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].C(Br)C.II.[C:37](=[O:39])=[O:38].[Cl-:40].[NH4+]>C1COCC1>[ClH:40].[CH2:25]([O:24][C:18]1[CH:19]=[CH:20][C:21]([C:37]([OH:39])=[O:38])=[CH:22][C:17]=1[C@@H:10]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:9][CH2:8][N:4]([CH:5]([CH3:7])[CH3:6])[CH:1]([CH3:3])[CH3:2])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 5

HCID 280Carbon DioxideHCID 807IodineHCID 6332Ethyl BromideHCID 25517Ammonium ChlorideHCID 24885301(R)-3-(2-benzyloxy)-5-bromophenyl)-N,N-diisopropyl-3-phenylpropan-1-amine2×

Product 1

HCID 66738888HCID 66738888, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the compound (R)—N,N-Diisopropyl-3-(2-benzyloxy-5-bromophenyl)-3-Phenylpropyl amine compound of formula (F) 25.8 Mg turnings, 400 ml THF, 0.87 g ethyl bromide and 3 crystal of iodine were added and reaction heated to 50° C. to 55° C. and further raised to 65° C. to 70° C. The reaction mass cooled to −60° C. to 70° C. and slowly added 200 g dry ice and stirred for 1 hour. Further the reaction temperature raised to −5° C. to 0° C. followed by slowly addition of 700 ml of 10% ammonium chloride solution. The reaction temperature raised to 25° C. to 35° C., maintained for 30 minutes and finally filtered and washed with 2×25 ml R.O. Water. Layers were separated and further aqueous layer was charged and cooled to 0° C. to 5° C. and adjusted pH at 1 to 2 using conc. Hydrochloric acid solution followed by addition 500 ml MDC. The reaction temperature was raised to 25° C. to 35° C. followed by separation of layers and MDC was distilled under vacuum below at 50° C. The reaction mass was cooled to 25° C. to 35° C. followed by addition of 50 ml of methanol+300 ml of diisopropylether and cooled to 0° C. to 5° C. and finally washed with 2×25 ml diisopropylether to afford the title compound (R)-4-benzyloxy-3-(3-diisopropylamino-1-phenylpropyl)-benzoic acid hydrochloride of formula (G).

Workup

  1. customreaction
  2. temperatureheated to 50° C. to 55° C.
  3. temperaturefurther raised to 65° C. to 70° C
  4. temperatureThe reaction mass cooled to −60° C. to 70° C.
  5. temperatureFurther the reaction temperature raised to −5° C. to 0° C.
  6. temperatureThe reaction temperature raised to 25° C. to 35° C.
  7. temperaturemaintained for 30 minutes
  8. filtrationfinally filtered
  9. washwashed with 2×25 ml R.O
  10. customLayers were separated
  11. additionfurther aqueous layer was charged
  12. temperaturecooled to 0° C. to 5° C.
  13. additionadjusted pH at 1 to 2 using conc. Hydrochloric acid solution followed by addition 500 ml MDC
  14. temperatureThe reaction temperature was raised to 25° C. to 35° C.
  15. customfollowed by separation of layers and MDC
  16. distillationwas distilled under vacuum below at 50° C
  17. temperatureThe reaction mass was cooled to 25° C. to 35° C.
  18. additionfollowed by addition of 50 ml of methanol+300 ml of diisopropylether
  19. temperaturecooled to 0° C. to 5° C.
  20. washfinally washed with 2×25 ml diisopropylether

Sources & evidence

ORD record
ord-ad256676151c48198ce91741ea0ede09
Source dataset
uspto-grants-2015_04
Patent number
US09012678B2

Reaction notes

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