2-Pyridinecarboxaldehyde → Tert-butyl 2-((8-(tert-butoxycarbonylamino)octyl)(pyridin-2-ylmethyl)amino)acetate

HRID 1509780Notes

Reaction equation

HRID 1509780 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14].[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH:24]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[C:40]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])(=[O:43])[CH:41]=O>ClCCCl.CC(O)=O>[C:13]([O:12][C:11]([NH:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:1]([CH2:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=1)[CH2:41][C:40]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])=[O:17])([CH3:14])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 142732-PyridinecarboxaldehydeHCID 4086223Tert-butyl (8-aminooctyl)carbamateHCID 5049666Sodium triacetoxyborohydrideHCID 10986247Tert-butyl 2-oxoacetate

Product 1

HCID 59404338Tert-butyl 2-((8-(tert-butoxycarbonylamino)octyl)(pyridin-2-ylmethyl)amino)acetateYield 58%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl 8-aminooctylcarbamate (1.61 g, 6.588 mmol), 2-pyridinecarboxaldehyde (0.63 mL, 6.588 mmol) and AcOH (0.10 mL) in DCE (30 mL) was heated at 75° C. for 30 min under nitrogen. The reaction mixture was cooled to 0° C., and treated sequentially with NaBH(OAc)3 (3.708 g, 17.5 mmol) and tert-butyl glyoxalate (1.53 g)1. The reaction mixture was stirred at room temperature overnight and quenched with water. The reaction mixture was then extracted with DCM and the organic layers was dried and concentrated under reduced pressure. The residue was purified by flash chromatography over silica gel to afford tert-butyl 2-((8-(tert-butoxycarbonylamino)octyl)(pyridin-2-ylmethyl)amino)acetate (1.71 g, 58%) as a yellow oil. 1H NMR (400 MHz, CD3Cl3) δ 8.52 (d, J=4.8 Hz, 1H), 7.65 (td, J=7.8, 1.6 Hz, 1H), 7.56 (d, J=7.6, 1H), 7.18-7.12 (m, 1H), 4.50 (s, 1H), 3.90 (s, 2H), 3.28 (s, 2H), 3.07 (q, J=6.3 Hz, 2H), 2.61 (t, J=7.6 Hz, 2H), 1.50-1.24 (m, 30H); ESMS m/z: 450.4 (M+H)+.

Workup

  1. customquenched with water
  2. extractionThe reaction mixture was then extracted with DCM
  3. customthe organic layers was dried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography over silica gel

Sources & evidence

ORD record
ord-2c7742aaa236405882ca39dc889355b0
Source dataset
uspto-grants-2012_07
Patent number
US08211402B2

Reaction notes

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