(S)-3-(tert-butyldimethylsilanyloxy)-1-(2-fluorophenyl)propylamine → 5-(3-bromophenyl)-N-[(1S)-3-[tert-butyl(dimethyl)silyl]oxy-1-(2-fluorophenyl)propyl]-5,6,6-trimethyl-4,4-dioxo-1,4,3-oxathiazin-2-amine

HRID 339874Notes

Reaction equation

HRID 339874 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2([CH3:20])[C:13]([CH3:15])([CH3:14])[O:12][C:11](OC)=[N:10][S:9]2(=[O:19])=[O:18])[CH:5]=[CH:6][CH:7]=1.[Si:21]([O:28][CH2:29][CH2:30][C@H:31]([NH2:39])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[F:38])([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2([CH3:20])[C:13]([CH3:15])([CH3:14])[O:12][C:11]([NH:39][C@H:31]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[F:38])[CH2:30][CH2:29][O:28][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:22])[CH3:23])=[N:10][S:9]2(=[O:19])=[O:18])[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 68292582(S)-3-(tert-butyldimethylsilanyloxy)-1-(2-fluorophenyl)propylamineHCID 683591715-(3-Bromophenyl)-2-methoxy-5,6,6-trimethyl-5,6-dihydro-1,4,3-oxathiazine 4,4-dioxide

Product 1

HCID 1784316875-(3-bromophenyl)-N-[(1S)-3-[tert-butyl(dimethyl)silyl]oxy-1-(2-fluorophenyl)propyl]-5,6,6-trimethyl-4,4-dioxo-1,4,3-oxathiazin-2-amineYield 64.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 188 mg of 5-(3-bromophenyl)-2-methoxy-5,6,6-trimethyl-5,6-dihydro-1,4,3-oxathiazine 4,4-dioxide and 157 mg of (S)-3-(tert-butyldimethylsilanyloxy)-1-(2-fluorophenyl)propylamine in 2 ml of methylene chloride was stirred at room temperature for 3 hours and the conversion was checked by LCMS. Since no reaction had taken place yet, the solvent was concentrated by rotary evaporation and the residue with addition of 0.25 ml of methylene chloride was stirred at room temperature for 17 hours. Subsequently, the reaction mixture was stirred at 50° C. for 4 hours. The crude product was purified by means of normal phase chromatography using a Flashmaster with an n-heptane/ethyl acetate gradient. The product-containing fractions were combined and concentrated by rotary evaporation. This gave the product (206 mg) with a molecular weight of 613.7 g/mol (C27H38BrFN2O4SSi); MS (ESI): m/e=614 (M+H+).

Workup

  1. concentrationthe solvent was concentrated by rotary evaporation
  2. additionthe residue with addition of 0.25 ml of methylene chloride
  3. stirringSubsequently, the reaction mixture was stirred at 50° C. for 4 hours
  4. customThe crude product was purified by means of normal phase chromatography
  5. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-a422ca920e3840609b821f72f596c5b8
Source dataset
uspto-grants-2014_11
Patent number
US08895547B2

Reaction notes

Loading…