Methanol → Tert-butyl 4-[4-(hydroxymethyl)-1,3-thiazol-2-yl]piperidine-1-carboxylate

HRID 660037Notes

Reaction equation

HRID 660037 reaction equation
C([O:3][C:4]([C:6]1[N:7]=[C:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[S:9][CH:10]=1)=O)C.[BH4-].[Li+].CO.O>C(OCC)C>[OH:3][CH2:4][C:6]1[N:7]=[C:8]([CH:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH2:16]2)[S:9][CH:10]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 2795532Ethyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylate2×HCID 4148881Lithium borohydride

Product 1

HCID 7164573Tert-butyl 4-[4-(hydroxymethyl)-1,3-thiazol-2-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A mixture of 1,1-dimethylethyl 4-[4-(ethoxycarbonyl)-2-thiazolyl]-1-piperidinecarboxylate (i.e. the product of Example 1, Step A) (3.4 g, 10 mmol), lithium borohydride (0.33 g, 15 mmol) and methanol (607 μL, 15 mmol) in diethyl ether (40 mL) was heated at reflux for 16 h. The reaction mixture was cooled, treated with water (5 mL) and extracted with diethyl ether and dichloromethane. The combined organic layers were dried (MgSO4) and concentrated under reduced pressure and purified by silica gel chromatography using 50-100% ethyl acetate in hexanes as eluant to give 1.72 g of the title compound as a white solid.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 16 h
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted with diethyl ether and dichloromethane
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-8505d73bb2a54c3d9e2e1b6cf1a0774b
Source dataset
uspto-grants-2011_12
Patent number
US08084468B2

Reaction notes

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