Triphenylphosphine → (R)-3-(1-(3-Bromophenyl)ethyl)-N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

HRID 920257Notes

Reaction equation

HRID 920257 reaction equation
[CH3:1][O:2][C:3]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:4]=1[CH2:5][N:6]([C:21]1[S:25][N:24]=[CH:23][N:22]=1)[S:7]([C:10]1[C:19]([F:20])=[CH:18][C:13]2[NH:14][C:15](=[O:17])[O:16][C:12]=2[CH:11]=1)(=[O:9])=[O:8].[Br:32][C:33]1[CH:34]=[C:35]([C@@H:39](O)[CH3:40])[CH:36]=[CH:37][CH:38]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.CCOC(C)=O.C(=O)(O)[O-].[Na+]>[Br:32][C:33]1[CH:34]=[C:35]([C@H:39]([N:14]2[C:13]3[CH:18]=[C:19]([F:20])[C:10]([S:7]([N:6]([CH2:5][C:4]4[CH:26]=[CH:27][C:28]([O:30][CH3:31])=[CH:29][C:3]=4[O:2][CH3:1])[C:21]4[S:25][N:24]=[CH:23][N:22]=4)(=[O:8])=[O:9])=[CH:11][C:12]=3[O:16][C:15]2=[O:17])[CH3:40])[CH:36]=[CH:37][CH:38]=1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 6951261(1S)-1-(3-bromophenyl)ethan-1-olHCID 89525954N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Product 1

HCID 89533765(R)-3-(1-(3-Bromophenyl)ethyl)-N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

Accordingly, the compound of Formula 28-1 ((R)-3-(1-(3-bromophenyl)ethyl)-N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide) was prepared from a solution provided by dissolving 2 g of the compound of Formula 11-3 (4.29 mmol, prepared as described above) and 0.862 g of (S)-1-(3-bromophenyl)ethanol (4.29 mmol) in 10 mL of THF. This solution was cooled to 0° C. and treated with triphenylphosphine (2.25 g, 8.58 mmol) followed by DEAD (1.36 mL, 8.58 mmol). After stirring at 0° C. for 120 min, the reaction mixture was diluted with EtOAc (50 mL) and sat'd sodium bicarbonate (10 mL), the aqueous layer was extracted with EtOAc (2×20 mL). The combined organics were washed with brine (10 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by normal phase chromatography (10-80% EtOAc in hexane) yielded the compound of Formula 28-1 as a solid which was used as isolated.

Workup

  1. customAccordingly, the compound of Formula 28-1 ((R)-3-(1-(3-bromophenyl)ethyl)-N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide) was prepared from a solution
  2. customprovided
  3. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  4. washThe combined organics were washed with brine (10 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by normal phase chromatography (10-80% EtOAc in hexane)

Sources & evidence

ORD record
ord-40d7f14fa1464129adabf1d20d5e6c93
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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