Triphenylphosphine → (1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected

HRID 2171283Notes

Reaction equation

HRID 2171283 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[C@H:21]1[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]1[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31].[N:35](C(OCC)=O)=NC(OCC)=O.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1>C1COCC1>[NH2:35][C@@H:21]1[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]1[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 199401P,P-Diphenylphosphinic azideHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 10013520(1S,2S)-trans-N-Boc-2-Aminocyclohexanol

Product 1

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedYield 52.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triphenylphosphine (14.3 g) was added to a THF (190 ml) solution containing tert-butyl ((1S,2S)-2-hydroxycyclohexyl)carbamate (10.0 g), followed by ice cooling. Diethyl azodicarboxylate (40% in toluene) (24.3 g) and DPPA (15.3 g) were added dropwise to the reaction solution, followed by stirring at room temperature for 1 hour. The reaction solution was left overnight. The solvent was distilled away under reduced pressure. Water was added and then a 20% sodium hydroxide aqueous solution was added. Then, the organic layers were collected. Water (30 ml) was added to the obtained organic layers, followed by heating to 60° C. A THF (40 ml) solution containing triphenylphosphine (14.3 g) was added dropwise, followed by reflux for 2.5 hours. The solvent was distilled away under ordinary pressure. Toluene was added and the pH was adjusted with 3M hydrochloric acid to pH=1 or less. Then, the resulting aqueous layers were collected, ethyl acetate was added, and the pH was adjusted with a 20% sodium hydroxide aqueous solution to pH 12. The organic layers were collected and dried over anhydrous sodium sulfate. Light yellow oily matter of tert-butyl ((1S,2R)-2-aminocyclohexyl)carbamate (5.24 g) was thus obtained.

Workup

  1. waitThe reaction solution was left overnight
  2. distillationThe solvent was distilled away under reduced pressure
  3. additionWater was added
  4. additiona 20% sodium hydroxide aqueous solution was added
  5. customThen, the organic layers were collected
  6. additionWater (30 ml) was added to the obtained organic layers
  7. temperatureby heating to 60° C
  8. additionA THF (40 ml) solution containing triphenylphosphine (14.3 g)
  9. additionwas added dropwise
  10. temperatureby reflux for 2.5 hours
  11. distillationThe solvent was distilled away under ordinary pressure
  12. additionToluene was added
  13. customThen, the resulting aqueous layers were collected
  14. additionethyl acetate was added
  15. customThe organic layers were collected
  16. dry with materialdried over anhydrous sodium sulfate

Sources & evidence

ORD record
ord-b889edee990f45bfba4903534925ac19
Source dataset
uspto-grants-2015_06
Patent number
US09051310B2

Reaction notes

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