1-(Benzyloxy)-2-bromobenzene → HCID 22622324, compound

HRID 840426Notes

Reaction equation

HRID 840426 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:16]([O:23][C:24]([N:26]1[CH2:31][CH2:30][C:29](=[O:32])[CH2:28][CH2:27]1)=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[OH:32][C:29]1([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:28][CH2:27][N:26]([C:24]([O:23][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:25])[CH2:31][CH2:30]1

Participants

3

Reactant 2

HCID 5618281-(Benzyloxy)-2-bromobenzeneHCID 643496Benzyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 22622324HCID 22622324, compoundYield 59%

Procedure

2-Benzyloxybromobenzene (242.3 g) was reacted with 1-benzyloxycarbonyl-4-piperidone (214.7 g) according to the method described for Example 2e to afford 4-hydroxy-4-(2-benzyloxyphenyl)-N-Cbz-piperidine (226.75 g) after extraction and chromatography using 10-30% ethyl acetate in hexanes. 1H NMR (300 MHz, CDCl3) δ 7.40-7.21 (m, 12H), 6.98 (m, 2H), 5.12 (s, 4H), 4.11 (br s, 3H), 3.35 (br s, 2H), 2.03 (br s, 4H). A sample of this material (235 g) was reacted with triethylsilane (405 mL) and trifluoroacetic acid (195 mL) according to the method described for Example 2f. Following extraction and chromatography (10-25% ethyl acetate in hexane), residual triethylsilane was removed by distillation (50-60° C., 800-900 millitorr) to afford 4-(2-benzyloxyphenyl)-N-Cbz-piperidine (179.3 g). A solution of this material (4.01 g) in ethanol (60 mL) was shaken for 24 h with palladium hydroxide on carbon [Pearlman's catalyst] (2.2 g) under hydrogen (50 psi). The catalyst was removed by filtration, the filtrate was concentrated and triturated with acetone to afford 4-(2-hydroxyphenyl)-piperidine (0.75 g) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ 8.49 (s, 1H), 7.02 (m, 2H), 6.82 (d, 1H), 6.72 (t, 1H), 3.20 (br d, 2H), 3.02 (m, 1H), 2.85 (tt, 2H), 1.74 (m, 4H). Using standard reductive amination conditions N-[2-(S)-(3,4-dichlorophenyl)]-4-oxobutyl-N-methyl-3-cyano-1-naphthamide (0.213 g) was reacted with 4-(2-hydroxyphenyl)-piperidine to afford N-[(S)-2-(3,4-dichlorophenyl)-4-[4-[2-hydroxyphenyl]-1-piperidinyl]butyl]-N-methyl-3-cyano-1-naphthamide.

Sources & evidence

ORD record
ord-1cd03dea50e64e3596d135523bea257f
Source dataset
uspto-grants-2002_04
Patent number
US06365602B1

Reaction notes

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