Acetic Acid → HCID 68576525, compound

HRID 2111918Notes

Reaction equation

HRID 2111918 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][C:30]2[S:34][C:33]([CH3:35])=[N:32][C:31]=2[CH3:36])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[CH:37]1([CH:40]=O)[CH2:39][CH2:38]1.C(O)(=O)C.[OH-].[Na+]>ClCCCl>[C:15]([O:19][C:20]([N:22]1[CH2:23][CH2:24][CH:25]([NH:28][CH:29]([CH2:40][CH:37]2[CH2:39][CH2:38]2)[C:30]2[S:34][C:33]([CH3:35])=[N:32][C:31]=2[CH3:36])[CH2:26][CH2:27]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 68576593HCID 68576593, compound

Product 1

HCID 68576525HCID 68576525, compoundYield 99.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (1.80 g, 8.49 mmol) is added to a stirred solution of 4-{[(2,4-dimethyl-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (1.71 g, 5.25 mmol), cyclopropanecarboxaldehyde (0.44 ml, 5.89 mmol), acetic acid (0.32 ml, 5.59 mmol), and 1,2-dichloroethane (35 ml). The reaction is stirred for 25 h at room temperature under nitrogen. The reaction is poured into 2N NaOH (100 ml) and extracted with ethyl acetate (100 ml×3). The ethyl acetate is dried over sodium sulfate and then the sodium sulfate is filtered off. The crude product is concentrated on a rotary evaporator and purified by flash chromatography on silica gel eluting with 40% ethyl acetate/hexanes to yield (1.98 g, 99%) of 4-{[cyclopropylmethyl-(2,4-dimethyl-thiazol-5-ylmethyl)]-amino}-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=380.3 (M+1); 1H NMR (CDCl3): δ=4.18 (2H, brs), 3.74 (2H, s), 2.86-2.78 (1H, m), 2.70-2.60 (5H, m), 2.41 (2H, d), 2.32 (3H, s), 1.81-1.70 (2H, m), 1.50-1.39 (11H, m), 0.87-0.80 (1H, m), 0.53-0.46 (2H, m), 0.12-0.06 (2H, m).

Workup

  1. extractionextracted with ethyl acetate (100 ml×3)
  2. dry with materialThe ethyl acetate is dried over sodium sulfate
  3. filtrationthe sodium sulfate is filtered off
  4. concentrationThe crude product is concentrated on a rotary evaporator
  5. custompurified by flash chromatography on silica gel eluting with 40% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-6066ca12f5a748e09cd85c580514356d
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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