tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate → Tert-butyl 4-(4-methoxy-3-methylbenzoyl)piperidine-1-carboxylate

HRID 1752236Notes

Reaction equation

HRID 1752236 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:19])N(OC)C)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([Mg]Br)=[CH:24][C:23]=1[CH3:30]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14](=[O:19])[C:25]2[CH:26]=[CH:27][C:22]([O:21][CH3:20])=[C:23]([CH3:30])[CH:24]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateHCID 178491913HCID 178491913, compound

Product 1

HCID 71212195Tert-butyl 4-(4-methoxy-3-methylbenzoyl)piperidine-1-carboxylateYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(methoxy-methyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (5.0 g, 18.36 mmol) in 50 mL dry THF at ambient temperature was added (4-methoxy-3-methylphenyl)magnesium bromide (55.1 mL, 0.5 M) was added dropwise under N2, the reaction mixture was stirred at the same temperature for 16 hours. The reaction was quenched with saturated sodium sulfate solution (10 mL) and partitioned between brine (150 mL) and 10% isopropyl alcohol/chloroform (200 mL), and the organic layer was removed to yield the crude product. Purification by flash chromatography (silica: 5-35% ethyl acetate/pentane) gave the title compound as a white solid (6.4 g, 19.21 mmol, >99% yield). HPLC (Novapak 150×3.9 mm C-18 column: mobile phase: 10-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 2 min.) retention time=4.131 min.

Workup

  1. additionwas added dropwise under N2
  2. customThe reaction was quenched with saturated sodium sulfate solution (10 mL)
  3. custompartitioned between brine (150 mL) and 10% isopropyl alcohol/chloroform (200 mL)
  4. customthe organic layer was removed
  5. customto yield the crude product
  6. customPurification by flash chromatography (silica: 5-35% ethyl acetate/pentane)

Sources & evidence

ORD record
ord-4fed1aa347e04fb6b9d445d76dc1fc86
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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