Sulfuric Acid → Di-tert-butyl ether

HRID 1010487Notes

Reaction equation

HRID 1010487 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 86621489HCID 86621489, compoundHCID 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-61ec91c9ea8c4d0fa9d0b521cb7c68e5
Source dataset
uspto-grants-2011_07
Patent number
US07973041B2

Reaction notes

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