Phosphorus oxychloride → 2-Chloro-4-((1R,2S)-2-hydroxy-1-(5-phenyloxazol-2-yl)propylamino)-3-methylbenzonitrile

HRID 563245Notes

Reaction equation

HRID 563245 reaction equation
P(Cl)(Cl)(Cl)=O.[Si]([O:13][C@@H:14]([CH3:39])[C@@H:15]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[C:31]([Cl:37])[C:30]=1[CH3:38])[C:16]([NH:18][CH2:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=O)(C(C)(C)C)(C)C>C1C=CC=CC=1>[Cl:37][C:31]1[C:30]([CH3:38])=[C:29]([NH:28][C@@H:15]([C:16]2[O:27][C:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:19][N:18]=2)[C@@H:14]([OH:13])[CH3:39])[CH:34]=[CH:33][C:32]=1[C:35]#[N:36]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 57908587(2R,3S)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-N-(2-oxo-2-phenylethyl)butanamide

Product 1

HCID 442011212-Chloro-4-((1R,2S)-2-hydroxy-1-(5-phenyloxazol-2-yl)propylamino)-3-methylbenzonitrileYield 4%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A 100 mL round bottomed flask was charged with phosphorous oxychloride (0.5 mL, 5.24 mmol) and benzene (20 mL). (2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-N-(2-oxo-2-phenylethyl)butanamide (1.14 g, 2.28 mmol) was then added to the mixture which was then placed under reflux for 4 h. The mixture was then concentrated en vacuo, then partitioned between EtOAc (40 mL) and a saturated solution of sodium bicarbonate (30 mL). The organic layer was washed with water (20 mL), dried (Na2SO4). Purification by flash column chromatography [hexanes/Et2O (3:2) as eluent] afforded the title compound as a white solid (30 mg, 4% yield). 1H NMR (500 MHz, CDCl3, δ in ppm) 7.59 (d, J=8 Hz, 2H), 7.32-7.42 (m, 4H), 7.28 (s, 1H), 6.58 (d, J=8 Hz, 1H), 5.17 (d, J=7 Hz, 1H), 4.93-4.95 (m, 1H), 4.66-4.75 (m, 1H), 2.40 (s, 3H) and 1.63 (d, J=6 Hz, 3H).

Workup

  1. temperatureunder reflux for 4 h
  2. concentrationThe mixture was then concentrated en vacuo
  3. custompartitioned between EtOAc (40 mL)
  4. washThe organic layer was washed with water (20 mL)
  5. dry with materialdried (Na2SO4)
  6. customPurification by flash column chromatography [hexanes/Et2O (3:2) as eluent]

Sources & evidence

ORD record
ord-cf57a5e9fd7e447899151a7c9bc85ff1
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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