Triphenylphosphine → (R)-N-(2,4-Dimethoxybenzyl)-3-(3-hydroxy-1-phenylpropyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

HRID 920272Notes

Reaction equation

HRID 920272 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:4]=1[CH2:5][N:6]([C:20]1[S:24][N:23]=[CH:22][N:21]=1)[S:7]([C:10]1[CH:19]=[CH:18][C:13]2[NH:14][C:15](=[O:17])[O:16][C:12]=2[CH:11]=1)(=[O:9])=[O:8].[C:31]1([C@@H:37](O)[CH2:38][CH2:39][OH:40])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=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+]>[CH3:1][O:2][C:3]1[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:4]=1[CH2:5][N:6]([C:20]1[S:24][N:23]=[CH:22][N:21]=1)[S:7]([C:10]1[CH:19]=[CH:18][C:13]2[N:14]([C@@H:37]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:38][CH2:39][OH:40])[C:15](=[O:17])[O:16][C:12]=2[CH:11]=1)(=[O:9])=[O:8]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 6950537(1S)-1-phenylpropane-1,3-diolHCID 89526027N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Product 1

HCID 117629301(R)-N-(2,4-Dimethoxybenzyl)-3-(3-hydroxy-1-phenylpropyl)-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 37-1 (N-(2,4-dimethoxybenzyl)-3-[(1R)-3-hydroxy-1-phenylpropyl]-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydro-1,3-benzoxazole-6-sulfonamide) was prepared from a solution provided by dissolving 200 mg of the compound of Formula 1-5 (0.429 mmol, prepared as described above) and (S)-1-phenylpropane-1,3-diol (65.3 mg, 0.429 mmol) (0.429 mmol) in 2 mL of THF. This solution was cooled to 0° C. and treated with triphenylphosphine (0.225 g, 0.858 mmol) followed by DEAD (0.136 mL, 0.858 mmol). After stirring at 0° C. for 120 min, the reaction mixture was diluted with EtOAc (50 mL) and saturated sodium bicarbonate (5 mL). The organic layer was 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 37-1 as a yellow oil which was used as isolated.

Workup

  1. customAccordingly, the compound of Formula 37-1 (N-(2,4-dimethoxybenzyl)-3-[(1R)-3-hydroxy-1-phenylpropyl]-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydro-1,3-benzoxazole-6-sulfonamide) was prepared from a solution
  2. customprovided
  3. washThe organic layer was washed with brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by normal phase chromatography (10-80% EtOAc in hexane)

Sources & evidence

ORD record
ord-14c7da05a8ef4826adb0e80b937486a6
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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