Dichloromethane → HCID 68577174, compound

HRID 2111925Notes

Reaction equation

HRID 2111925 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH:28][CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[S:34]1[CH:38]=[CH:37][N:36]=[C:35]1[CH:39]=O.ClCCl>C(OCC)(=O)C>[C:15]([O:19][C:20]([N:22]1[CH2:23][CH2:24][CH:25]([N:28]([CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32])[CH2:39][C:35]2[S:34][CH:38]=[CH:37][N:36]=2)[CH2:26][CH2:27]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 27349031,3-Thiazole-2-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 43652145HCID 43652145, compound

Product 1

HCID 68577174HCID 68577174, compoundYield 76.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Sodium triacetoxyborohydride (0:30 g, 1.42 mmol) is added to a stirred solution of 4-(3-methyl-butylamino)-piperidine-1-carboxylic acid tert-butyl ester (0.19 g, 0.71 mmol), 2-thiazolecarboxaldehyde (0.12 ml, 1.42 mmol), and dichloromethane (3.5 ml). The reaction is stirred overnight at room temperature under nitrogen. The reaction is diluted with ethyl acetate, washed with aqueous saturated NaHCO3, dried over Na2SO4, filtered, and concentrated. Water is added to the residue, and the solution loaded onto a SCX-2 (10 g) column and washed with water (20 ml) and methanol (20 ml). The product is then eluted with 2M ammonia in methanol (30 ml). The filtrate is concentrated and the crude material purified on silica gel eluting with 0-50% ethyl acetate/hexanes to yield (0.20 g) of 4-{(3-methyl-butyl)-[(thiazol-2-yl)-methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=368 (M+1); 1H NMR (CDCl3): δ=7.67 (1H, d), 7.23 (1H, d), 4.17 (2H, brs), 3.93 (2H, s), 2.72-2.54 (5H, m), 1.78 (2H, brd), 1.7-1.57 (2H, m), 1.45-1.41 (10H, m), 1.40-1.32 (2H, m), 0.87 (6H, d).

Workup

  1. washwashed with aqueous saturated NaHCO3
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionWater is added to the residue
  6. washwashed with water (20 ml) and methanol (20 ml)
  7. washThe product is then eluted with 2M ammonia in methanol (30 ml)
  8. concentrationThe filtrate is concentrated
  9. customthe crude material purified on silica gel eluting with 0-50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-2364e6dd9aff4992a6dd5bb2aaf0d10a
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

Loading…