Dimethylformamide → HCID 59643968, compound

HRID 2252429Notes

Reaction equation

HRID 2252429 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[N:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:10](=[O:18])[C@@H:9]2[CH2:19][CH2:20][C@H:21]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[C:4]([OH:37])[CH:3]=1.CN(C)C=O.N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:57]([C:60]([CH3:63])([CH3:62])[CH3:61])([CH3:59])[CH3:58])(=O)=O>ClCCl.C(OCC)(=O)C.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[N:11]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:10](=[O:18])[C@@H:9]2[CH2:19][CH2:20][C@H:21]([O:29][Si:30]([C:33]([CH3:34])([CH3:36])[CH3:35])([CH3:32])[CH3:31])[C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)=[C:4]([O:37][Si:57]([C:60]([CH3:63])([CH3:62])[CH3:61])([CH3:59])[CH3:58])[CH:3]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 79372,6-Lutidine2×HCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonate2×HCID 59643934(3R,4S)-4-(4-bromo-2-hydroxyphenyl)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-1-phenylazetidin-2-one

Product 1

HCID 59643968HCID 59643968, compoundYield 99%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3R,4S)-4-(4-Bromo-2-hydroxyphenyl)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-1-phenylazetidin-2-one (1.04 g, 1.79 mmol) was dissolved in anhydrous dichloromethane (5 mL), anhydrous N,N-dimethylformamide (5 mL) and stirred under nitrogen at room temperature. 2,6-Lutidine (1.0 mL, 920 mg, 8.6 mmol) was added followed by drop-wise addition of tert-butyldimethylsilyl trifluromethane sulfonate (1.2 mL, 1.38 g, 5.22 mmol). The reaction was stirred under nitrogen at room temperature for 2.25 h. 2,6-Lutidine (0.25 mL, 230 mg, 2.15 mmol) was added followed by addition of tert-butyldimethylsilyl trifluromethane sulfonate (0.4 mL, 460 mg, 1.74 mmol) and after a total of 4.5 h at room temperature the reaction was diluted with ethyl acetate and water and the layers were separated. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with 0.5 N hydrochloric acid, saturated sodium bicarbonate solution, water (4 times) and brine, dried over sodium sulfate, filtered, concentrated and purified by chromatography (40 g silica gel, 1% to 85% ethyl acetate-hexane) to afford (3R,4S)-4-(4-bromo-2-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-1-phenylazetidin-2-one (1.23 g, 99% yield); Rf 0.57 (1:4 ethyl acetate-hexane); 1H NMR (300 MHz, CDCl3) δ 7.33-7.14 (m, 6H), 7.09-6.91 (m, 6H), 4.99 (d, J=2.3 Hz, 1H), 4.62 (t, J=5.6 Hz, 1H), 3.06 (ddd, J=4.9, 2.5, 2.3 Hz, 1H), 1.97-1.69 (m, 4H), 1.03 (s, 9H), 0.84 (s, 9H), 0.33 (s, 3H), 0.29 (s, 3H), −0.01 (s, 3H), −0.20 (s, 3H) ppm.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with 0.5 N hydrochloric acid, saturated sodium bicarbonate solution, water (4 times) and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by chromatography (40 g silica gel, 1% to 85% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-970d772e11d64db0adee22c4fcc76d91
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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