Triphenylphosphine → (1S,3S,4S)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine (1R,3R,4R)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine

HRID 1963906Notes

Reaction equation

HRID 1963906 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:34]([N:41]([CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[C@H:42]1[CH2:47][CH2:46][C@@H:45](O)[C@@H:44]([CH3:49])[CH2:43]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[CH2:57]([N:64]([CH2:73][C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1)[C@@H:65]1[CH2:70][CH2:69][C@H:68](O)[C@H:67]([CH3:72])[CH2:66]1)[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1.P([N:96]=[N+:97]=[N-:98])(=O)(OC1C=CC=CC=1)OC1C=CC=CC=1>C1COCC1.CCOC(C)=O.[Cl-].[Na+].O>[N:96]([C@H:45]1[CH2:46][CH2:47][C@H:42]([N:41]([CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:43][C@@H:44]1[CH3:49])=[N+:97]=[N-:98].[N:96]([C@@H:68]1[CH2:69][CH2:70][C@@H:65]([N:64]([CH2:73][C:74]2[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=2)[CH2:57][C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)[CH2:66][C@H:67]1[CH3:72])=[N+:97]=[N-:98]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 123414Diphenylphosphoryl azideHCID 5363146Diisopropyl azodicarboxylateHCID 68277691(1R,2S,4S)-4-(dibenzylamino)-2-methylcyclohexanol (1S,2R,4R)-4-(dibenzylamino)-2-methylcyclohexanol

Product 1

HCID 86650616(1S,3S,4S)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine (1R,3R,4R)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of DIAD (5.03 mL, 25.9 mmol) and triphenylphosphine (6.78 g, 25.9 mmol) in THF (35 mL) was allowed to form a salt. After 30 min a solution of (1R,2S,4S)-4-(dibenzylamino)-2-methylcyclohexanol/(1S,2R,4R)-4-(dibenzylamino)-2-methylcyclohexanol (2 g, 6.46 mmol) and diphenyl phosphorazidate (2.507 mL, 11.63 mmol) in THF (25 mL) was added and the mixture was stirred for 20 hr at 55° C. The mixture was cooled to ambient temperature and diluted with EtOAc and brine. The separated organic layer was dried over Na2SO4, filtered off and concentrated in vacuo providing crude (1S,3S ,4S)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine/(1R,3R,4R)-4-azido-N,N-dibenzyl-3-methylcyclohexanamine as orange oil, which was directly used in the next step without further purification. LCMS (m/z): 335.1 [M+H]+; Retention time=0.81 min.

Workup

  1. customto form a salt
  2. temperatureThe mixture was cooled to ambient temperature
  3. dry with materialThe separated organic layer was dried over Na2SO4
  4. filtrationfiltered off
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-85ddc5a1f5f2405b862e1c3cdb6dc45f
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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