Trimethyl borate → Cyclopropyl-(4-hydroxymethyl-piperidin-1-yl)-methanone

HRID 5138

Reaction equation

HRID 5138 reaction equation
[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][CH:9]([C:12](OCC)=[O:13])[CH2:8][CH2:7]2)=[O:5])[CH2:3][CH2:2]1.[BH4-].[Li+].B(OC)(OC)OC>O1CCCC1.O>[CH:1]1([C:4]([N:6]2[CH2:7][CH2:8][CH:9]([CH2:12][OH:13])[CH2:10][CH2:11]2)=[O:5])[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 8470Trimethyl borateHCID 4148881Lithium borohydrideHCID 10036613Ethyl 1-(cyclopropylcarbonyl)piperidine-4-carboxylate

Product 1

HCID 10012597Cyclopropyl-(4-hydroxymethyl-piperidin-1-yl)-methanoneYield 63.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1-(cyclopropylcarbonyl)-4-carboethoxy piperidine (35 g, 156 mmol) in anhydrous tetrahydrofuran (350 mL) was stirred at ambient temperature under a nitrogen atmosphere. A solution of lithium borohydride in tetrahydrofuran (2M, 78 mL, 156 mmol) was added dropwise. Trimethyl borate (1.77 mL, 15.7 mmol) was added, then the reduction mixture was stirred for about 48 hours. Water was added dropwise with vigorous stirring until the vigorous gas evolution ceased. The mixture was diluted twofold with water and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. Vacuum distillation (bp 165° C., 0.5 mm Hg) gave a clear, colorless liquid (18.2 g): IR (neat): 3410 (br, s), 3094 (w), 3008 (s), 2918 (s), 2858 (s), 1738 (m), 1613 (s), 1448 (s), 1375 (s), 1316 (s); 1H-NMR: 4.7-4.5 (m, 1H), 4.4-4.1 (m, 1H), 3.6-3.4 (m, 2H), 3.2-2.5 (m, 3H), 2.0-1.7 (m, 4H), 1.4-1.1 (m, 1H), 1.0-0.8 (m, 2H), 0.8-0.65 (m, 2H); HRMS: Calcd for C10H17NO2 :183.1259; Found: 183.1250; Anal.: Calcd for C10H17NO2 :C, 65.54, H, 9.35, N, 7.64; Found: C, 65.83, H, 9.43, N, 7.50.

Workup

  1. stirringwith vigorous stirring until the vigorous gas evolution
  2. extractionextracted three times with ethyl acetate
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. distillationVacuum distillation (bp 165° C., 0.5 mm Hg)

Sources & evidence

ORD record
ord-832f1035ccee4e16b54fec29013e82eb
Source dataset
uspto-grants-1993_09
Patent number
US05243048

Linked notes

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