Dimethylformamide → 1-(Tert-butoxycarbonyl)-4-isocyanato-4-phenylpiperidine

HRID 1172220Notes

Reaction equation

HRID 1172220 reaction equation
C(N(CC)CC)C.[N-]=[N+]=[N-].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][C:21]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)(C(O)=O)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C[N:34]([CH:36]=[O:37])C>>[C:11]([O:15][C:16]([N:18]1[CH2:19][CH2:20][C:21]([N:34]=[C:36]=[O:37])([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:22][CH2:23]1)=[O:17])([CH3:13])([CH3:14])[CH3:12]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 33558AzideHCID 7369171-((Tert-butoxy)carbonyl)-4-phenylpiperidine-4-carboxylic acid

Product 1

HCID 184143761-(Tert-butoxycarbonyl)-4-isocyanato-4-phenylpiperidine

Procedure

Triethylamine (5.02 mL, 36.1 mmol) and diphenylhosphoryl azide (4.24 mL, 19.7 mmol) are added to a solution of 1-(tert-butoxycarbonyl)-4-phenyl-4-piperidinecarboxylic acid (5.0 g, 16.4 mmol) in dry DMF (50 mL) under nitrogen at ambient temperature. The mixture is stirred at ambient temperature for 2 h, and then heated to 60° C. for 3 h. The mixture is slightly cooled and concentrated in vacuo. Water (75 mL) is added to the remanence followed by extraction with ethyl acetate (2×75 mL). Combined organic fractions are washed with brine (3×50 mL), dried (MgSO4) and evaporated to dryness. The crude mixture is purified by silica gel chromatography eluting with ethyl acetate-heptane (1:4). This furnishes 4.8 g (98%) of the wanted 1-(tert-butoxycarbonyl)-4-isocyanato-4-phenyl-piperidine as a clear oil. LC/MS (m/z) 203.2 (M-boc+H+); tR=3.64 min. 1H NMR (CDCl3) 1.49 (s, 9H); 1.92 (bd, 2H); 2.02 (dt, 2H); 3.15 (bt, 2H); 4.17 (bs, 2H); 7.26 (dd, 1H); 7.39 (dt, 2H); 7.44 (dd, 2H).

Workup

  1. temperatureheated to 60° C. for 3 h
  2. temperatureThe mixture is slightly cooled
  3. concentrationconcentrated in vacuo
  4. additionWater (75 mL) is added to the remanence
  5. extractionfollowed by extraction with ethyl acetate (2×75 mL)
  6. washCombined organic fractions are washed with brine (3×50 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated to dryness
  9. customThe crude mixture is purified by silica gel chromatography
  10. washeluting with ethyl acetate-heptane (1:4)

Sources & evidence

ORD record
ord-2ef47c4cb64145fcbe073e03b3d5f04e
Source dataset
uspto-grants-2010_11
Patent number
US07834008B2

Reaction notes

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