Ethyl Acetate → HCID 89955560, compound

HRID 1481304Notes

Reaction equation

HRID 1481304 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]([O:11][CH3:12])=[O:10])[CH:5]=[CH:4][C:3]=1[C:13]1[N:14]=[C:15]([C@@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:27][CH:28]=[CH2:29])[N:16]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:17]=1.CCN([CH:44]([CH3:46])[CH3:45])C(C)C.[CH3:47]CCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.[C:65](OCC)(=[O:67])C>>[CH3:12][O:11][C:9]([NH:8][C:6]1[CH:5]=[CH:4][C:3]([C:13]2[N:14]=[C:15]([C@@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:27][CH:28]=[CH2:29])[N:16]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:17]=2)=[C:2]([NH:1][C:65](=[O:67])[C@H:44]([CH3:45])[CH:46]=[CH2:47])[CH:7]=1)=[O:10]

Participants

5

Reactant 4

HCID 8857Ethyl Acetate2×HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 66744061HCID 66744061, compound

Product 1

HCID 89955560HCID 89955560, compoundYield 81%

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.), clear yellow orange solution of 135D (4.83 g, 9.08 mmol) in ethyl acetate (91 ml) was added Intermediate 10 (1.0 g, 9.99 mmol) and Hunig's base (6.34 ml, 36.3 mmol). Next, 1-propanephosphonic acid cyclic anhydride (T3P) (50% in EtOAc) (13.38 ml, 22.70 mmol) was added dropwise over 20 min and the reaction was stirred at 0° C. After 3 h, the reaction was diluted with EtOAc and washed with sat. NaHCO3. The aqueous layer was extracted with EtOAc (2×). The organic layers were combined and washed with brine, dried over sodium sulfate, filtered and concentrated to give an orange foam. Purification by normal phase chromatography gave 135E (4.53 g, 81% yield) as a white foam. Proton NMR indicated a 3:1 mixture of diastereomers. MS (ESI) m/z: 614.4 (M+H)±.

Workup

  1. washwashed with sat. NaHCO3
  2. extractionThe aqueous layer was extracted with EtOAc (2×)
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give an orange foam
  8. customPurification by normal phase chromatography

Sources & evidence

ORD record
ord-9016230b3fbf41f3a3a5c1589472ae75
Source dataset
uspto-grants-2016_08
Patent number
US09409908B2

Reaction notes

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