3,4-Dichlorophenol → 1-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(3,4-dichlorophenoxy)piperidine hydrochloride

HRID 745329Notes

Reaction equation

HRID 745329 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH2:9][CH2:10][CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([OH:18])[CH2:14][CH2:13]3)=[N:7][O:8][C:4]=2[CH:3]=1.[Cl:21][C:22]1[CH:23]=[C:24](O)[CH:25]=[CH:26][C:27]=1[Cl:28].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1C=CC=CC=1>[ClH:21].[F:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH2:9][CH2:10][CH2:11][N:12]3[CH2:13][CH2:14][CH:15]([O:18][C:25]4[CH:24]=[CH:23][C:22]([Cl:21])=[C:27]([Cl:28])[CH:26]=4)[CH2:16][CH2:17]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 72583,4-DichlorophenolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 133198661-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-hydroxypiperidine

Product 1

HCID 133198631-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(3,4-dichlorophenoxy)piperidine hydrochloride

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

To a solution of 6.4 g of 1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-hydroxypiperidine, 3.7 g of 3,4-dichlorophenol and 6.6 g of triphenylphosphine in 200 ml of benzene, cooled with an ice bath, was slowly added over one hr a solution of 4.4 g of diethyl azodicarboxylate in 50 ml of benzene. After stirring twenty hrs at ambient temperature, the reaction mixture was filtered and the filtrate was concentrated. The residue was treated with ethereal hydrogen chloride to yield a salt. The salt was rebasified to given an oil, which was purified by column chromatography (silica gel, tetrahydrofuran). The purified oil was treated with ethereal hydrogen chloride, and the resultant salt was recrystallized from ethyl acetate/methanol to give 2.4 g (23%) or product, mp 212°-214° C.

Workup

  1. filtrationthe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated
  3. additionThe residue was treated with ethereal hydrogen chloride
  4. customto yield a salt
  5. customwas purified by column chromatography (silica gel, tetrahydrofuran)
  6. additionThe purified oil was treated with ethereal hydrogen chloride
  7. customthe resultant salt was recrystallized from ethyl acetate/methanol
  8. customto give 2.4 g (23%) or product, mp 212°-214° C.

Sources & evidence

ORD record
ord-9bb1e8b6545c4959bc94892dbbd15cd5
Source dataset
uspto-grants-1986_07
Patent number
US04598152

Reaction notes

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