Sulfuric Acid → Di-tert-butyl ether

HRID 1726697Notes

Reaction equation

HRID 1726697 reaction equation
C(N1[CH2:13][C@@H:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:11][C@H](C(OC)=O)[C@H]1C(OCC1C=CC=CC=1)=O)C1C=CC=CC=1.[CH3:33]C(=C)C.C(N1C[C@@H](O)C[C@H](C(OC)=O)[C@H]1C(OCC1C=CC=CC=1)=O)C1C=CC=CC=1.S(=O)(=O)(O)O>>[C:15]([O:14][C:12]([CH3:11])([CH3:13])[CH3:33])([CH3:16])([CH3:17])[CH3:18]

Participants

5

Reactant 4

HCID 1118Sulfuric AcidHCID 8255Isobutylene2×HCID 866214892-benzyl 3-methyl (2S,3S,5S)-1-benzyl-5-tert-butoxypiperidine-2,3-dicarboxylateHCID 866214902-benzyl 3-methyl(2S,3S,5S)-1-benzyl-5-hydroxypiperidine-2,3-dicarboxylate

Product 1

HCID 22541Di-tert-butyl etherYield 51%

Procedure

Part 1. 2-benzyl 3-methyl(2S, 3S, 5S)-1-benzyl-5-tert-butoxypiperidine-2,3-dicarboxylate: Isobutylene (2.96 mL, 0.0313 mol) was collected at −78 Celsius. To the cold isobutylene was added 2-benzyl 3-methyl(2S,3S,5S)-1-benzyl-5-hydroxypiperidine-2,3-dicarboxylate (0.60 g, 0.0016 mol) tetrahydrofuran (3.00 mL, 0.0370 mol), sulfuric acid (0.021 mL, 0.00039 mol). The reaction was sealed and allowed to warm up to rt and stirred at rt overnight. The mixture was cooled to −78 Celsius again. The seal was replaced with a septa connecting with a balloon. The reaction was then allowed to warm up to rt gradually to allow the evaporating of excess isobutylene. The residue was diluted with EtOAc, neutralized with aq. sodium hydroxide. The organic layers were washed with brine, dried. The residue was purified on silica gel, eluting with 0 to 30% EtOAc in hexane, to afford the tert-butyl ether (0.35 g, 51%). MS (ESI): (M+H)+=440.25.

Workup

  1. customThe reaction was sealed
  2. temperatureThe mixture was cooled to −78 Celsius again
  3. temperatureto warm up to rt gradually
  4. customevaporating of excess isobutylene
  5. additionThe residue was diluted with EtOAc
  6. washThe organic layers were washed with brine
  7. customdried
  8. customThe residue was purified on silica gel
  9. washeluting with 0 to 30% EtOAc in hexane

Sources & evidence

ORD record
ord-a15d5cf3446c4565bc40291261d3a030
Source dataset
uspto-grants-2009_02
Patent number
US07491724B2

Reaction notes

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