Hydrochloric Acid → HCID 178462327, compound

HRID 2303320Notes

Reaction equation

HRID 2303320 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:21][CH2:20][CH2:19][N:18]([CH2:22][C:23]3[N:24]=[N:25][NH:26][C:27]=3[CH2:28][N:29]([CH3:31])[CH3:30])[C@H:17]2[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[ClH:41].CCCCCCC>C(OCC)(=O)C.C(O)(C)C.O>[ClH:41].[F:40][C:2]([F:1])([F:39])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:21][CH2:20][CH2:19][N:18]([CH2:22][C:23]3[N:24]=[N:25][NH:26][C:27]=3[CH2:28][N:29]([CH3:30])[CH3:31])[C@H:17]2[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 8900Heptane2×HCID 178462326HCID 178462326, compound

Product 1

HCID 178462327HCID 178462327, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolvent4×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)-ethoxy)-4-(5-(dimethylamino)methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)-morpholine (1.417 kg, 2.46 mol) in ethyl acetate (7.5 L) at room temperature is added a solution of HCl in isopropanol (approx. 495 mL). The end point was monitored by taking 1 mL solution, diluting with 2 mL IPA and 2 mL of water and checking its pH, to a preferred end point of 4.6˜4.8. After reaching its end point, an additional amount of isopropanol (255 mL) was added to bring the total volume of isopropanol to 750 mL. Heptane (4 L) was added followed by seed of Form I. The mixture was aged for two hours, then additional heptane (20.75 L) was added over a period of 6 hours and the mixture was aged for 16 hours before filtering. The resulting solid was collected by filtration and the cake was washed with ethyl acetatelheptane (5 L, 1/2 mixture) and then dried to afford 1.32 kg of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)-ethoxy)4-(5-(dimethylamino)methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluoro-phenyl)morpholine hydrochloride.

Workup

  1. waitthe mixture was aged for 16 hours
  2. filtrationbefore filtering
  3. filtrationThe resulting solid was collected by filtration
  4. washthe cake was washed with ethyl acetatelheptane (5 L, 1/2 mixture)
  5. customdried

Sources & evidence

ORD record
ord-fe2f4823f37a461bbaa5ef330b6754dd
Source dataset
uspto-grants-2002_08
Patent number
US06432952B1

Reaction notes

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