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

HRID 1623331Notes

Reaction equation

HRID 1623331 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-0e8a8c9e07e5430194227639ceb19770
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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