Hydrochloric Acid → Sarizotan Hydrochloride

HRID 1825290Notes

Reaction equation

HRID 1825290 reaction equation
[ClH:1].[NH2:2][CH2:3][C@H:4]1[CH2:13][CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[O:5]1.[O-]CC.[Na+].[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:26]=[C:27]([CH:31]=O)[CH:28]=[N:29][CH:30]=2)=[CH:21][CH:20]=1.[BH4-].[Na+].Cl>C(O)C.O>[ClH:1].[F:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[CH:26]=[C:27]([CH2:31][NH:2][CH2:3][C@H:4]3[CH2:13][CH2:12][C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[O:5]3)[CH:28]=[N:29][CH:30]=2)=[CH:23][CH:24]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 4311764Sodium borohydrideHCID 98776715-(4-Fluorophenyl)pyridine-3-carbaldehydeHCID 55250747(R)-chroman-2-ylmethanamine hydrochloride

Product 1

HCID 6918387Sarizotan HydrochlorideYield 69.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

20.3 g of (R)-2-aminomethylchroman hydrochloride are introduced into 150 ml of ethanol, and 36.8 g of a 20% solution of sodium ethoxide in ethanol are added dropwise with stirring. 20.5 g of 5-(4-fluorophenyl)pyridine-3-carbaldehyde are added to the suspension at 35° C., and the mixture is stirred for a further 3 hours. After addition of 4.2 g of sodium borohydride, the mixture is stirred for a further 4 hours, and 62 ml of water are then added dropwise at room temperature. The pH of the reaction mixture is then adjusted to pH 4 using 37% hydrochloric acid over the course of one hour. The crystals are filtered off, rinsed with ethanol and dried under reduced pressure, giving 27.2 g of (R)-(−)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]chroman hydrochloride (69% yield).

Workup

  1. additionare added dropwise
  2. stirringthe mixture is stirred for a further 3 hours
  3. stirringthe mixture is stirred for a further 4 hours
  4. customover the course of one hour
  5. filtrationThe crystals are filtered off
  6. washrinsed with ethanol
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-fc3c587b531c40d794a02f6e48f8da08
Source dataset
uspto-grants-2006_05
Patent number
US07045629B2

Reaction notes

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