Benzoic Acid → HCID 131733418, compound

HRID 2275020Notes

Reaction equation

HRID 2275020 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[C:34]([O:38][C:39]([NH:41][C@H:42]1[C@H:47]([OH:48])[CH2:46][CH2:45][N:44]([C:49]([O:51][CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)=[O:50])[CH2:43]1)=[O:40])([CH3:37])([CH3:36])[CH3:35].[C:59](O)(=[O:66])[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1>O1CCCC1>[C:59]([O:48][C@H:47]1[CH2:46][CH2:45][N:44]([C:49]([O:51][CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)=[O:50])[CH2:43][C@H:42]1[NH:41][C:39]([O:38][C:34]([CH3:37])([CH3:35])[CH3:36])=[O:40])(=[O:66])[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1

Participants

6

Reactant 4

HCID 243Benzoic AcidHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 53487823Benzyl (3R,4R)-3-(tert-butoxycarbonylamino)-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 131733418HCID 131733418, compoundYield 96.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of triphenylphosphine (5.83 g, 22.24 mmol) in tetrahydrofuran (THF) (60 mL) was added DIAD (4.38 mL, 22.24 mmol) and the mixture was stirred in an ice-water bath for 15 min and then allowed to warm to rt. To the suspension was added a suspension of trans-benzyl 3-((tert-butoxycarbonyl)amino)-4-hydroxypiperidine-1-carboxylate (6.495 g, 18.54 mmol) in tetrahydrofuran (THF) (75 mL) followed by benzoic acid (2.72 g, 22.24 mmol). The reaction mixture cleared to a yellow solution and was stirred for 2 h. LCMS analysis showed product formation, however the SM peak was obscured by by-product so it was difficult to confirm reaction had gone to completion. The reaction was left to stir overnight (20 h). The reaction mixture was concentrated under vacuum. The residue was purified by silica chromotagraphy. The residue was loaded in DCM on a 340 g silica cartridge and purified using a 0-40% EtOAc/cyclohexane gradient. The appropriate fractions were combined and the evaporated in vacuo to give the crude product cis-benzyl 4-(benzoyloxy)-3-((tert-butoxycarbonyl)amino)piperidine-1-carboxylate (8.11 g, 17.84 mmol, 96% yield) as a pale yellow oil.

Workup

  1. additionTo the suspension was added
  2. stirringwas stirred for 2 h
  3. customreaction
  4. waitThe reaction was left
  5. stirringto stir overnight (20 h)
  6. concentrationThe reaction mixture was concentrated under vacuum
  7. customThe residue was purified by silica chromotagraphy
  8. custompurified
  9. customthe evaporated in vacuo

Sources & evidence

ORD record
ord-1b6ef82d45a9420689966fb44bbbe96b
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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