Phosphorus oxychloride → HCID 86726359, compound

HRID 629756Notes

Reaction equation

HRID 629756 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:33])[C:7]=1[CH2:8][CH2:9][C@H:10]1[O:15][CH2:14][C@H:13]([CH2:16][O:17][C:18]([NH:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[O:19])[N:12]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:11]1.[N:34]([C@@H:37]([C@H:41]([C:49]1[CH:54]=[C:53]([F:55])[CH:52]=[C:51]([F:56])[CH:50]=1)[C:42]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=1)[C:38](O)=[O:39])=[N+:35]=[N-:36].O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[N:34]([C@@H:37]([C@@H:41]([C:42]1[CH:43]=[CH:44][C:45]([F:48])=[CH:46][CH:47]=1)[C:49]1[CH:50]=[C:51]([F:56])[CH:52]=[C:53]([F:55])[CH:54]=1)[C:38]([NH:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:33])[C:7]=1[CH2:8][CH2:9][C@H:10]1[O:15][CH2:14][C@H:13]([CH2:16][O:17][C:18]([NH:20][CH2:21][C:22]([F:25])([F:23])[F:24])=[O:19])[N:12]([C:26]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:27])[CH2:11]1)=[O:39])=[N+:35]=[N-:36]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 86726352HCID 86726352, compoundHCID 86726357HCID 86726357, compound

Product 1

HCID 86726359HCID 86726359, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of tert-butyl (2R,5R)-2-(2-(3-amino-5-fluoropyridin-4-yl)ethyl)-5-(2,2,2-trifluoroethylaminocarbonyloxymethyl)morpholine-4-carboxylate (Example 89, step 4) (64 mg, 0.13 mmol) and (2S,3S)-2-azido-3-(3,5-difluorophenyl)-3-(4-fluorophenyl)propanoic acid (43 mg, 0.13 mmol) in pyridine (0.5 mL) was cooled to −10° C. in an ice-acetone bath. To the stirred solution was added POCl3 (0.014 mL, 0.15 mmol) and the mixture was stirred for 30 min. The reaction was quenched by the addition of aqueous NaHCO3 solution and the resulting mixture was extracted with two portions of EtOAc. The combined EtOAc layers were dried (MgSO4), filtered, and the solvents were removed in vacuo. The residue was chromatographed on a 12 g SiO2 column using a gradient elution of 0-80% EtOAc in hexanes. Fractions containing product were combined and the solvents were removed in vacuo to give a gum. LC MS: RT=1.48 min, M+H=784 (2 min gradient)

Workup

  1. customThe reaction was quenched by the addition of aqueous NaHCO3 solution
  2. extractionthe resulting mixture was extracted with two portions of EtOAc
  3. dry with materialThe combined EtOAc layers were dried (MgSO4)
  4. filtrationfiltered
  5. customthe solvents were removed in vacuo
  6. customThe residue was chromatographed on a 12 g SiO2 column
  7. washa gradient elution of 0-80% EtOAc in hexanes
  8. additionFractions containing product
  9. customthe solvents were removed in vacuo
  10. customto give a gum
  11. customRT=1.48 min, M+H=784 (2 min gradient)

Sources & evidence

ORD record
ord-5bfb9521cb3f4dd18c81922ed261d438
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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