Hydrochloric Acid → Raloxifene Hydrochloride

HRID 1702196Notes

Reaction equation

HRID 1702196 reaction equation
[ClH:1].[N:2]1([CH2:8][CH2:9][O:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C[O:21][C:22]1[CH:23]=[CH:24][C:25]2[CH:29]=[C:28]([C:30]3[CH:35]=[CH:34][C:33]([O:36]C)=[CH:32][CH:31]=3)[S:27][C:26]=2[CH:38]=1.[Cl-].[Al+3].[Cl-].[Cl-].[I-].[Li+].C(S)C.Cl>O.O1CCCC1.ClCCl>[ClH:1].[OH:21][C:22]1[CH:23]=[CH:24][C:25]2[C:29]([C:15](=[O:17])[C:14]3[CH:13]=[CH:12][C:11]([O:10][CH2:9][CH2:8][N:2]4[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]4)=[CH:19][CH:18]=3)=[C:28]([C:30]3[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=3)[S:27][C:26]=2[CH:38]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 6343EthanethiolHCID 66321Lithium iodideHCID 8509416-Methoxy-2-(4-methoxyphenyl)benzo[b]thiopheneHCID 57438354-(2-Piperidinoethoxy)benzoic acid hydrochlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 54900Raloxifene Hydrochloride

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

The acid chloride was made from 1.5 g. of 4-(2-piperidinoethoxy)benzoic acid, hydrochloride, as described in Example 1. To the acid chloride were added 30 ml. of dichloromethane, 1.35 g. of 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene and 5 g. of aluminum chloride. The mixture was stirred at ambient temperature for 2.5 hours, and then 0.74 g. of lithium iodide was added. The mixture was stirred for 1 hour, and then 0.68 g. of ethanethiol was added and the mixture was stirred for 30 minutes more at a temperature between 25° and 35°. The reaction was then worked up by the addition of 25 ml. of tetrahydrofuran, 5 ml. of 20% hydrochloric acid and 50 ml. of water. The mixture was stirred overnight and was filtered. The solids were washed with 45 ml. of water and then with 40 ml. of diethyl ether, and the product was vacuum dried. The yield was 2.18 g. of product, which was found by 90 mHz nmr analysis to be substantially identical to the product of Example 1.

Workup

  1. stirringThe mixture was stirred for 1 hour
  2. stirringthe mixture was stirred for 30 minutes more at a temperature between 25° and 35°
  3. additionThe reaction was then worked up by the addition of 25 ml
  4. stirringThe mixture was stirred overnight
  5. filtrationwas filtered
  6. washThe solids were washed with 45 ml
  7. customdried

Sources & evidence

ORD record
ord-4ca5f8b8953e43a1b663ca477f4a5d6d
Source dataset
uspto-grants-1983_04
Patent number
US04380635

Reaction notes

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