Sodium Carbonate → tert-Butyl ((1r,4r)-4-((3-(pyridin-4-yl)benzyl)amino)cyclohexyl)carbamate

HRID 885024Notes

Reaction equation

HRID 885024 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][CH:14]=2)[CH:10]=O)=[CH:3][CH:2]=1.[C:15]([O:19][C:20](=[O:29])[NH:21][CH:22]1[CH2:27][CH2:26][CH:25]([NH2:28])[CH2:24][CH2:23]1)([CH3:18])([CH3:17])[CH3:16].[BH4-].[Na+].C([O-])([O-])=O.[Na+].[Na+]>CO>[C:15]([O:19][C:20](=[O:29])[NH:21][CH:22]1[CH2:23][CH2:24][CH:25]([NH:28][CH2:10][C:9]2[CH:12]=[CH:13][CH:14]=[C:7]([C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)[CH:8]=2)[CH2:26][CH2:27]1)([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 2756050Cis tert-Butyl 4-aminocyclohexylcarbamateHCID 27955633-(pyridin-4-yl)benzaldehydeHCID 4311764Sodium borohydride

Product 1

HCID 59201760tert-Butyl ((1r,4r)-4-((3-(pyridin-4-yl)benzyl)amino)cyclohexyl)carbamateYield 95%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-pyridinyl benzaldehyde (10) (205 mg, 1.1 mmol) in methanol (20 ml) was added NT-Boc-1,4-diaminocyclohexane (6) (300 mg, 1.4 mmol), and the mixture was stirred at room temperature for 30 min. To this solution was added NaBH4 (0.5 g, 13.2 mmol) in portions at 0° C., and the reaction mixture was stirred at room temperature overnight. The reaction was worked up by addition of saturated aqueous Na2CO3 (2 ml), and the mixture was then extracted with chloroform (3×6 ml). The combined organic layers were dried over anhydrous MgSO4. The solvent was removed under vacuum and the residue was purified by a flash chromatography on silica gel (CH2Cl2/MeOH=10/1) to give 18 (398 mg) in 95% yield; 1H NMR (300 MHz, CDCl3): 8.66 (d, J=8.1 Hz, 2H), 7.39-7.61 (m, 6H), 4.30-4.50 (br, 1H), 3.88 (s, 2H), 3.30-3.50 (br, 1H), 2.40-2.60 (m, 1H), 1.90-2.10 (m, 4H), 1.70-1.90 (br, 1H), 1.44 (s, 9H), 1.06-1.40 (m, 4H) 13C NMR (75 MHz, CDCl3): 155.2, 150.0, 148.3, 141.5, 138.1, 129.1, 128.7, 126.6, 125.5, 121.6, 79.0, 55.6, 51.0, 49.4, 31.9, 28.3; HRMS (ESI) calcd for C23H31N3O2 (M+H+) 382.24890; found 382.24896.

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. extractionthe mixture was then extracted with chloroform (3×6 ml)
  3. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  4. customThe solvent was removed under vacuum
  5. customthe residue was purified by a flash chromatography on silica gel (CH2Cl2/MeOH=10/1)

Sources & evidence

ORD record
ord-a2728b3b354548f6b022abace63614eb
Source dataset
uspto-grants-2012_08
Patent number
US08242142B2

Reaction notes

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