Pivalaldehyde → HCID 86614127, compound

HRID 20034Notes

Reaction equation

HRID 20034 reaction equation
[CH2:1]([N:4]([C:8]([CH3:11])([CH3:10])[CH3:9])[C:5](=[O:7])[O-:6])[CH:2]=[CH2:3].Br[C:13]1[CH:14]=[C:15]2[C@@H:22]([NH2:23])[CH2:21][C:20]3([CH2:26][CH2:25][CH2:24]3)[O:19][C:16]2=[N:17][CH:18]=1.C([Li])(C)(C)C.[CH:32](=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34]>CCOCC>[CH2:1]([N:4]([C:8]([CH3:11])([CH3:10])[CH3:9])[C:5](=[O:6])[O-:7])[CH:2]=[CH2:3].[OH:37][CH:32]([C:13]1[CH:14]=[C:15]2[C@@H:22]([NH2:23])[CH2:21][C:20]3([CH2:26][CH2:25][CH2:24]3)[O:19][C:16]2=[N:17][CH:18]=1)[C:33]([CH3:36])([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 12417PivalaldehydeHCID 86614128N-allyl-N-t-butylcarbamate (4'S)-6'-(bromo)-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridin]-4'-amineHCID 178418306HCID 178418306, compound

Product 1

HCID 86614127HCID 86614127, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of N-allyl-N-t-butylcarbamate-(4′S)-6′-(bromo)-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-b]pyridin]-4′-amine (4.12 g, 10.1 mmol) in ether (80 mL) was cooled to −78° C. and then t-butyllithium (12.5 ml, 21.3 mmol) was added and stirred for 15 minutes before the pivalaldehyde (3.80 ml, 35.0 mmol) (Note: freshly distilled) was added. After 5 minutes, LC-MS shows the starting material has been consumed. The reaction was quenched with sat'd NH4Cl and the organic layer separated. The organic layer was combined with previous trial reactions and adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (120 g), eluting with 0% to 30% EtOAc in hexane, to provide N-allyl-N-t-butylcarbamate-(4′S)-6′-(1-hydroxy-2,2-dimethylpropyl)-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-b]pyridin]-4′-amine as a yellow oil. MS m/z: 417 (M+1).

Workup

  1. distillationfreshly distilled)
  2. additionwas added
  3. customhas been consumed
  4. customThe reaction was quenched with sat'd NH4Cl
  5. customthe organic layer separated
  6. customchromatographed through a Redi-Sep® pre-packed silica gel column (120 g)
  7. washeluting with 0% to 30% EtOAc in hexane

Sources & evidence

ORD record
ord-29ac4f6b875e4486bd0070afcbcd2da9
Source dataset
uspto-grants-2010_06
Patent number
US07745484B2

Reaction notes

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