tert-Butanol → HCID 68535128, compound

HRID 401809Notes

Reaction equation

HRID 401809 reaction equation
[O:1]=[C:2]1[CH2:7][CH:6]2[CH2:8][CH2:9][CH:3]1[CH2:4][CH:5]2C(O)=O.CC[N:15]([CH2:18]C)CC.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:27])C=CC=CC=1.[C:37]([OH:41])([CH3:40])([CH3:39])[CH3:38]>>[C:37]([O:41][C:18](=[O:27])[NH:15][CH:5]1[CH2:4][CH:3]2[CH2:9][CH2:8][CH:6]1[CH2:7][C:2]2=[O:1])([CH3:40])([CH3:39])[CH3:38]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 68531723HCID 68531723, compound

Product 1

HCID 68535128HCID 68535128, compoundYield 63%

Conditions

Temperature
17 °C

Procedure

5-Oxo-bicyclo[2.2.2]octane-2-carboxylic acid (Preparation 74, 314 g, 1.87 mol, 1.0 eq) was taken up in tert-butanol (1.8 L) and cooled to 17° C. Et3N (289 mL, 2.06 mol, 1.1 eq) was added dropwise while the temperature was kept below 21° C. After addition, the reaction mixture was stirred for an additional 90 minutes before diphenylphosphoryl azide (405 mL, 1.87 mol, 1.0 eq) was added in a dropwise fashion over 45 minutes while nitrogen gas evolves. After addition the reaction mixture was heated to 40° C. with a waterbath overnight and more nitrogen gas evolved. The reaction mixture was heated to reflux for 5½ hours after which the mixture was concentrated to ˜1.5 L at 55° C. The residue was parted between water (2.0 L) and tert-butyl methyl ether (1.0 L). The aqueous layer was extracted with tert-butyl methyl ether (4×500 mL). The combined organic layers were washed with water (500 mL), 1M sodium hydroxide solution (500 mL) and water (500 mL). The combined aqueous layers were extracted with diethyl ether (500 mL). The combined organic layers were dried over sodium sulfate and concentrated at 40° C. to give a tan solid (279 g, 1.17 mol, 63%).

Workup

  1. customwas kept below 21° C
  2. additionAfter addition
  3. additionwas added in a dropwise fashion over 45 minutes while nitrogen gas evolves
  4. additionAfter addition the reaction mixture
  5. temperaturewas heated to 40° C. with a waterbath overnight
  6. temperatureThe reaction mixture was heated
  7. temperatureto reflux for 5½ hours after which the mixture
  8. concentrationwas concentrated to ˜1.5 L at 55° C
  9. extractionThe aqueous layer was extracted with tert-butyl methyl ether (4×500 mL)
  10. washThe combined organic layers were washed with water (500 mL), 1M sodium hydroxide solution (500 mL) and water (500 mL)
  11. extractionThe combined aqueous layers were extracted with diethyl ether (500 mL)
  12. dry with materialThe combined organic layers were dried over sodium sulfate
  13. concentrationconcentrated at 40° C.

Sources & evidence

ORD record
ord-3db2dfb69f224fe69d394953a7db950d
Source dataset
uspto-grants-2014_06
Patent number
US08741934B2

Reaction notes

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