Triethylamine → [(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-(4-methoxy-benzyl)-amine

HRID 1186181Notes

Reaction equation

HRID 1186181 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:22])=[C:6]([C@:8]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)([CH3:11])[CH2:9][OH:10])[CH:7]=1.C(N(CC)CC)C.[C:30]([Si:34]([CH3:37])([CH3:36])Cl)([CH3:33])([CH3:32])[CH3:31]>ClCCl.CN(C)C1C=CN=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:22])=[C:6]([C@:8]([NH:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)([CH3:11])[CH2:9][O:10][Si:34]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:37])[CH3:36])[CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chlorideHCID 66931632(R)-2-(5-bromo-2-fluoro-phenyl)-2-(4-methoxy-benzylamino)-propan-1-ol

Product 1

HCID 66931457[(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-(4-methoxy-benzyl)-amine

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-2-(5-bromo-2-fluoro-phenyl)-2-(4-methoxy-benzylamino)-propan-1-ol (6.95 g, 18.9 mmol) in dichloromethane (170 ml) was treated at room temperature with triethylamine (5.78 ml, 41.5 mmol), 4-dimethylaminopyridine (1.15 g, 9.43 mmol), and tert-butyldimethylchlorosilane (1.15 g, 37.7 mmol). After 16 hours at room temperature the reaction mixture was consecutively extracted with saturated sodium hydrogen carbonate solution (100 ml), water (100 ml), and brine (100 ml). The aqueous layers were re-extracted with dichloromethane (100 ml). The combined organic layers were dried over sodium sulfate and evaporated at reduced pressure. After chromatography on Silicycle-Si-amine column using heptane as the eluent, [(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-(4-methoxy-benzyl)-amine (intermediate C8A) was obtained as a colourless oil (8.0 g, 88% of theory). MS (ISP): m/z=482.2, 484.3 [M+H]+.

Workup

  1. extractionAfter 16 hours at room temperature the reaction mixture was consecutively extracted with saturated sodium hydrogen carbonate solution (100 ml), water (100 ml), and brine (100 ml)
  2. extractionThe aqueous layers were re-extracted with dichloromethane (100 ml)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. customevaporated at reduced pressure

Sources & evidence

ORD record
ord-6dc0a8fbb0d0404fbb96cbdfeabc4f38
Source dataset
uspto-grants-2014_03
Patent number
US08673894B2

Reaction notes

Loading…