Triphenylphosphine → HCID 69670026, compound

HRID 1943592Notes

Reaction equation

HRID 1943592 reaction equation
[OH:1][CH:2]1[CH2:5][C:4]2([CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][CH2:6]2)[CH2:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:37][C:38]1[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[C:41](O)=[CH:40][CH:39]=1.N(C(OCC)=O)=NC(OCC)=O.[OH-].[Na+]>C1(C)C=CC=CC=1>[ClH:37].[Cl:37][C:38]1[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[C:41]([O:1][CH:2]2[CH2:3][C:4]3([CH2:6][CH2:7][NH:8][CH2:9][CH2:10]3)[CH2:5]2)=[CH:40][CH:39]=1

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 117874-Chloro-1-naphtholHCID 14798Sodium HydroxideHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 9834677Tert-butyl 2-hydroxy-7-azaspiro[3.5]nonane-7-carboxylate

Product 1

HCID 69670026HCID 69670026, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

Under an inert atmosphere, 1.00 g (4.14 mmoles) of tert-butyl 2-hydroxy-7-aza-spiro[3.5]-nonane-7-carboxylate (WO 2003084948) is dissolved in 41 ml of toluene. 1.250 g (4.77 mmoles) of triphenylphosphine and 0.888 g (4.97 mmoles) of 4-chloronaphthalen-1-ol (commercial) are added. The medium is cooled to 0° C. and a solution of 0.794 g (4.56 mmoles) of diethyl azodicarboxylate in 3 ml of toluene is added. The medium is stirred for 14 hrs at ambient temperature, then concentrated under vacuum. The residue obtained is taken up in a 1N aqueous solution of caustic soda and extracted twice with dichloromethane. The combined organic phases are washed once with a saturated aqueous solution of sodium chloride, dried over sodium sulphate, filtered and concentrated under vacuum. The crude residue is taken up in 20 ml of dichloromethane and 10 ml (40 mmoles) of a 4N solution of hydrochloric acid in dioxan are added slowly with stirring. After stirring for 3 hrs at ambient temperature, the medium is concentrated under vacuum and the residue is taken up in a 1N aqueous solution of hydrochloric acid. The aqueous phase is extracted twice with ethyl acetate then slowly basified to pH 10 by addition of 35% caustic soda solution. The aqueous phase is extracted three times with dichloromethane. These three organic extracts are combined, washed once with a saturated aqueous solution of sodium chloride, dried over sodium sulphate, filtered and concentrated under vacuum. The expected product is obtained in the form of a wax which is taken up in 2 ml of a 4N solution of hydrochloric acid in dioxan. The medium is diluted with diethyl ether and the precipitate formed is filtered off, rinsed with diethyl ether and dried under vacuum. 1.10 g of the hydrochloride of the expected product is obtained in the form of a white powder.

Workup

  1. concentrationconcentrated under vacuum
  2. customThe residue obtained
  3. extractionextracted twice with dichloromethane
  4. washThe combined organic phases are washed once with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. addition10 ml (40 mmoles) of a 4N solution of hydrochloric acid in dioxan are added slowly
  9. stirringwith stirring
  10. stirringAfter stirring for 3 hrs at ambient temperature
  11. concentrationthe medium is concentrated under vacuum
  12. extractionThe aqueous phase is extracted twice with ethyl acetate
  13. additionthen slowly basified to pH 10 by addition of 35% caustic soda solution
  14. extractionThe aqueous phase is extracted three times with dichloromethane
  15. washwashed once with a saturated aqueous solution of sodium chloride
  16. dry with materialdried over sodium sulphate
  17. filtrationfiltered
  18. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-6b6f52adb39947d5a29ceb95b9aead7e
Source dataset
uspto-grants-2013_03
Patent number
US08394787B2

Reaction notes

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