2'-Hydroxyacetophenone → Tert-butyl 4-oxo-3,4-dihydrospiro[1-benzopyran-2,4'-piperidine]-1'-carboxylate

HRID 229504Notes

Reaction equation

HRID 229504 reaction equation
N1CCC2(C=CC3C=CC=CC=3O2)CC1.[OH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23](=[O:25])[CH3:24].[C:26]([N:33]1[CH2:38][CH2:37][C:36](=O)[CH2:35][CH2:34]1)([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].N1CCCC1>CO>[C:26]([N:33]1[CH2:34][CH2:35][C:36]2([CH2:24][C:23](=[O:25])[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[O:16]2)[CH2:37][CH2:38]1)([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27]

Participants

6

Reactant 4

HCID 83752'-HydroxyacetophenoneHCID 31268PyrrolidineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 18770935Spiro[chromene-2,4'-piperidine]

Product 1

HCID 40427565Tert-butyl 4-oxo-3,4-dihydrospiro[1-benzopyran-2,4'-piperidine]-1'-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The compounds prepared in Examples Z1-Z14 and depicted in Table Z1 were prepared according to the Schemes Z1-Z6. The preparation of spiro[2H-1-benzopyran-2,4′-piperidine] derivatives 15 (Example Z1), 16 (Example Z2) and 18 (Example Z3) is outlined in Scheme Z1. The 2′-hydroxyacetophenone derivatives 1, 2 and 3 (commercially available from Aldrich Chemical Company) were condensed with 1-Boc-4-piperidone 4 in methanol in the presence of pyrrolidine to provide N-Boc-spiro[2H-1-benzopyran-2,4′-piperidine]-4(3H)-one derivatives 5-7 respectively. Compounds 12-14 were prepared by conversion of the ketones 5-7 to the enol triflate derivatives 8-10 and subsequent Suzuki coupling reaction with 4-(N,N-diethylaminocarbonyl)phenylboronic acid 11. The Boc protecting groups of 12-14 were subsequently removed using trifluoroacetic acid to generate the corresponding spiro[2H-1-benzopyran-2,4′-piperidine] derivatives 15 (Example Z1), 16 (Example Z2) and 17. Demethylation of the methyl ether 17 using boron tribromide in anhydrous dichloromethane afforded the phenolic derivative 18 (Example Z3). Hydrogenation of 15 in methanol in the presence of palladium hydroxide (Pearlman's catalyst) afforded the 3,4-dihydrospiro[2H,1-benzopyran-2,4′-piperidine] derivative 19 (Example Z4) (Scheme Z2). Treatment of 15 with formaldehyde in the presence of sodium cyanoborohydride gave the N-methyl derivative 20 (Example Z5) (Scheme Z2).

Workup

  1. customwere prepared

Sources & evidence

ORD record
ord-8bedaf7d2efb42a9894d26e4f9e39090
Source dataset
uspto-grants-2009_07
Patent number
US07563802B2

Reaction notes

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