Acetyl chloride → 1-[3-Bromo-6-(1-(tert-butoxycarbonyl)-4-piperidinyloxy)-2-fluoro-phenyl]-3-trimethylsilyoxy-2-aza-1,3-butadiene

HRID 1095075Notes

Reaction equation

HRID 1095075 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[C:17]([F:22])[C:16]=2C=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O[C:30]([N:32]1CCC(COC2C=CC(I)=CC=2C=O)[CH2:34][CH2:33]1)=O)(C)(C)C.[CH3:49][Si:50](N[Si](C)(C)C)([CH3:52])[CH3:51].C([Li])CCC.C[Si](Cl)(C)C.C(N(CC)CC)C.C(Cl)(=[O:77])C>>[Br:21][C:18]1[C:17]([F:22])=[C:16]([CH:30]=[N:32][C:33]([O:77][Si:50]([CH3:52])([CH3:51])[CH3:49])=[CH2:34])[C:15]([O:14][CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2)=[CH:20][CH:19]=1

Participants

8

Reactant 7

HCID 6367Acetyl chlorideHCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 13838HexamethyldisilazaneHCID 577431634-(2-Formyl-4-iodo-phenoxymethyl)-piperidine-1-carboxylic acid tert-butyl esterHCID 577434454-(4-Bromo-3-fluoro-2-formyl-phenoxy)-piperidine-1-carboxylic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 666415521-[3-Bromo-6-(1-(tert-butoxycarbonyl)-4-piperidinyloxy)-2-fluoro-phenyl]-3-trimethylsilyoxy-2-aza-1,3-butadiene

Procedure

In a manner similar to the method described in example 1d, 4-(4-bromo-3-fluoro-2-formyl-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester (4.22 g, 10.5 mmol) was used as the starting material in place of 4-(2-formyl-4-iodo-phenoxymethyl)-piperidine-1-carboxylic acid tert-butyl ester to react with 1,1,3,3,3-hexamethyldisilazane (2.18 mL, 10.5 mmol), n-butyllithium (2.5 M, 4.2 mL, 10.5 mmol), trimethylsilyl chloride (1.33 mL, 10.5 mmol), triethylamine (1.9 mL, 13.6 mmol) and acetyl chloride (0.97 mL, 13.6 mmol) to give crude 1-[3-bromo-6-(1-(tert-butoxycarbonyl)-4-piperidinyloxy)-2-fluoro-phenyl]-3-trimethylsilyoxy-2-aza-1,3-butadiene as a yellow gum and used for the next step without further purification.

Sources & evidence

ORD record
ord-7071bfb965794ca1be57d30e9d6c0998
Source dataset
uspto-grants-2012_03
Patent number
US08134001B2

Reaction notes

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