Sodium Bicarbonate → tert-butyl (1S,2S,4S)-4-(dibenzylamino)-2-methylcyclohexylcarbamate tert-butyl (1R,2R,4R)-4-(dibenzylamino)-2-methylcyclohexylcarbamate

HRID 1963908Notes

Reaction equation

HRID 1963908 reaction equation
[CH2:1]([N:8]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C@H:9]1[CH2:14][CH2:13][C@H:12]([NH2:15])[C@@H:11]([CH3:16])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:24]([N:31]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C@@H:32]1[CH2:37][CH2:36][C@@H:35]([NH2:38])[C@H:34]([CH3:39])[CH2:33]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[C:47]([O-:50])([OH:49])=[O:48].[Na+]>O1CCOCC1>[CH2:17]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@H:9]1[CH2:14][CH2:13][C@H:12]([NH:15][C:47](=[O:48])[O:49][C:25]([CH3:30])([CH3:26])[CH3:24])[C@@H:11]([CH3:16])[CH2:10]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH2:40]([N:31]([CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[C@@H:32]1[CH2:37][CH2:36][C@@H:35]([NH:38][C:47](=[O:48])[O:50][C:2]([CH3:7])([CH3:3])[CH3:1])[C@H:34]([CH3:39])[CH2:33]1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 86650619(1S,3S,4S)-N1,N1-dibenzyl-3-methylcyclohexane-1,4-diamine (1R,3R,4R)-N1,N1-dibenzyl-3-methylcyclohexane-1,4-diamine

Product 1

HCID 86650621tert-butyl (1S,2S,4S)-4-(dibenzylamino)-2-methylcyclohexylcarbamate tert-butyl (1R,2R,4R)-4-(dibenzylamino)-2-methylcyclohexylcarbamate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To (1S,3S ,4S)—N1,N1-dibenzyl-3-methylcyclohexane-1,4-diamine/(1R,3R,4R)—N1,N1-dibenzyl-3-methylcyclohexane-1,4-diamine (1.851 g, 6 mmol) in dioxane (200 mL) and saturated aqueous NaHCO3 solution (100 mL) was added BOC-anhydride (2.438 mL, 10.50 mmol), dissolved in dioxane (˜5 mL). The resulting white suspension was stirred vigorously for 18 hr. The mixture was extracted with DCM (4×300 mL) and EtOAc (1×100 mL). The combined organic layers were concentrated in vacuo. The resulting residue was dissolved in EtOAc, washed with brine, dried over Na2SO4, filtered of and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 120 g, DCM/MeOH= 100/0 to 95/5]. Fractions containing product were combined, concentrated in vacuo providing tert-butyl (1S,2S,4S)-4-(dibenzylamino)-2-methylcyclohexylcarbamate/tert-butyl (1R,2R,4R)-4-(dibenzylamino)-2-methylcyclohexylcarbamate. Yield: 778 mg. LCMS (m/z): 409.2 [M+H]+; Retention time=0.84 min.

Workup

  1. extractionThe mixture was extracted with DCM (4×300 mL) and EtOAc (1×100 mL)
  2. concentrationThe combined organic layers were concentrated in vacuo
  3. dissolutionThe resulting residue was dissolved in EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered of and
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by column chromatography [SiO2, 120 g, DCM/MeOH= 100/0 to 95/5]
  9. additionFractions containing product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bb59a8eea6a64903b4f9eb7c75a321f7
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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