Water → HCID 57884066, compound

HRID 1817929Notes

Reaction equation

HRID 1817929 reaction equation
Cl.CN.[N:4]1([C:9](=[O:29])[CH2:10][C@H:11]([C:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][C:25]=3[O:27][CH3:28])[NH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)C=CN=[CH:5]1.O>C(O)(C)C>[CH3:28][O:27][C:25]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:26]=1[C:18]([C@H:11]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:10][C:9]([NH:4][CH3:5])=[O:29])=[CH:19][NH:20]2

Participants

5

Reactant 3

HCID 962WaterHCID 6364545Methylamine hydrochlorideHCID 57884063HCID 57884063, compound

Product 1

HCID 57884066HCID 57884066, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
22 °C

Procedure

Methylamine hydrochloride (2.04 kg) was added, and the reactor contents were stirred at 22 degrees C. overnight. A 10 mL aliquot of the reactor contents was taken, from which HPLC indicated completion (<1% of (S)-1-Imidazol-1-yl-3-(4-methoxy-1H-indol-3-yl)-3-phenyl-propan-1-one) of the reaction. Cold tap water (64 L) was added, followed by isopropyl alcohol (8.2 kg). The reactor was set up for atmospheric distillation, and the reactor jacket was heated at 85 degrees C. and methylene chloride was removed by distillation until the reactor temperature reached 70 degrees C. The reactor was gradually cooled to 22 degrees C. and the resulting slurry was stirred for one hour. The product was filtered on a Nutsche filter, and the collected solid was washed with water-isopropyl alcohol (1:1) and dried at 70 degrees C. to afford (S)-3-(4-methoxy-1H-indol-3-yl)-N-methyl-3-phenyl-propionamide as an off-white crystalline solid, (7.094 kg, 98% yield). 1H nmr (DMSO-d6): 2.48 (d, 3H, J=4.56 Hz), 2.60-2.90 (m, 2H), 3.69 (s, 3H), 5.05 (t, 1H, J=7.95 Hz), 6.34 (m, 1H), 6.90 (m, 2H), 7.08 (m, 2H), 7.20 (m, 4H), 7.75 (bq, 1H, J=4.56 Hz), 10.8 (bs, 1H). Mp=178-181° C.

Workup

  1. customovernight
  2. distillationThe reactor was set up for atmospheric distillation
  3. temperaturethe reactor jacket was heated at 85 degrees C
  4. customand methylene chloride was removed by distillation until the reactor temperature
  5. customreached 70 degrees C
  6. temperatureThe reactor was gradually cooled to 22 degrees C
  7. stirringand the resulting slurry was stirred for one hour
  8. filtrationThe product was filtered on a Nutsche
  9. filtrationfilter
  10. washthe collected solid was washed with water-isopropyl alcohol (1:1)
  11. customdried at 70 degrees C

Sources & evidence

ORD record
ord-ce9bd4e9aecb4da18d5c36b080a3523e
Source dataset
uspto-grants-2009_10
Patent number
US07598399B2

Reaction notes

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