tert-Butanol → HCID 59013943, compound

HRID 907533

Reaction equation

HRID 907533 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19](Cl)=[N:18][CH:17]=[CH:16][N:15]=2)[CH:10]([CH3:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:22]1[CH:27]=[CH:26][C:25]([CH2:28][OH:29])=[CH:24][CH:23]=1.C(C(CCC)[O-])(C)(C)C.[K+].C(O)(C)(C)C>O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([O:29][CH2:28][C:25]3[CH:26]=[CH:27][N:22]=[CH:23][CH:24]=3)=[N:18][CH:17]=[CH:16][N:15]=2)[CH:10]([CH3:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 114724-HydroxymethylpyridineHCID 21908991Tert-butyl 4-(3-chloropyrazin-2-yl)-3-methylpiperazine-1-carboxylateHCID 23710422Potassium tert-butylbutoxide

Product 1

HCID 59013943HCID 59013943, compoundYield 81.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

3′-Chloro-2-methyl-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (1.88 g, 6.0 mmol), pyridin-4-yl-methanol (1.35 g, 12.4 mmol) and a solution of 1M potassium tert-butyl butoxide in tert-butyl alcohol (14 mL, 14 mmol) were combined and stirred at room temperature overnight. The reaction mixture is diluted with H2O and washed with EtOAc (3×). The combined EtOAc extractions were washed with 6% NaHCO3 (2×), sat's NaCl (1×), dried (Na2SO4), and concentrated in vacuo. The crude product was purified by column chromatography (4:1 hexanes:EtOAc, followed by 1:1 hexanes:EtOAc) to give 1.89 g (81%) of 2-methyl-3′-(pyridin-4-ylmethoxy)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester. 1H NMR (CDCl3) 8.06 (d, 2H), 7.75 (d, 1H), 7.51 (d, 1H), 7.30 (d, 2H), 5.42 (s, 2H), 4.52 (m, 1H), 4.11-3.81 (complex m, 3H), 3.36-3.11 (complex m, 3H), 1.48 (s, 9H), 1.17 (d, 3H) ppm. LC-MS (MH+)=386.

Workup

  1. washwashed with EtOAc (3×)
  2. extractionThe combined EtOAc extractions
  3. washwere washed with 6% NaHCO3 (2×), sat's NaCl (1×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography (4:1 hexanes:EtOAc, followed by 1:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-d2e2e5de3d624fa0b3c2ccc74d18c1dd
Source dataset
uspto-grants-2011_09
Patent number
US08013156B2

Linked notes

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