Triethylamine → 2,2-Dimethyl-propionic acid (3S,4S)-1-[(S)-2-(4-tert-butoxycarbonylamino-piperidin-1-yl)-1-methyl-ethyl]-3-methyl-piperidin-4-yl ester

HRID 1929011Notes

Reaction equation

HRID 1929011 reaction equation
O[C@H:2](C)[CH2:3][N:4]1[CH2:9][CH2:8][C@H:7]([O:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])[C@@H:6]([CH3:17])[CH2:5]1.[CH2:19]([N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])C.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[C:41]([O:45][C:46](=[O:54])[NH:47][CH:48]1CCNCC1)([CH3:44])([CH3:43])[CH3:42]>C(Cl)Cl>[C:41]([O:45][C:46]([NH:47][CH:48]1[CH2:25][CH2:24][N:21]([CH2:19][C@@H:3]([N:4]2[CH2:9][CH2:8][C@H:7]([O:10][C:11](=[O:16])[C:12]([CH3:13])([CH3:14])[CH3:15])[C@@H:6]([CH3:17])[CH2:5]2)[CH3:2])[CH2:22][CH2:23]1)=[O:54])([CH3:44])([CH3:43])[CH3:42]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 67749Trifluoromethanesulfonic anhydrideHCID 7238334-(N-Boc-amino)piperidineHCID 66841391HCID 66841391, compound

Product 1

HCID 668419902,2-Dimethyl-propionic acid (3S,4S)-1-[(S)-2-(4-tert-butoxycarbonylamino-piperidin-1-yl)-1-methyl-ethyl]-3-methyl-piperidin-4-yl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of alcohol 57 (1.26 g, 5.16 mmol) and triethylamine (1.43 ml, 10.32 mmol) in 80 ml of DCM is cooled to −78 C. Triflic anhydride (0.85 ml, 5.16 mmol) is slowly added and stirring continued for 1 hour. The mixture is then allowed to warm up to 0 C and cooled back to −78 C after 15 minutes. A solution of piperidin-4-yl-carbamic acid tert-butyl ester, 3, (1.03 g, 5.16 mmol) in 40 ml of DCM is slowly added at −78 C. After complete addition, the cooling bath is removed and the dark solution is allowed to warm up to room temperature. The mixture is washed twice with water, dried over sodium sulphate, filtered and evaporated. The crude is purified by chromatography on silicagel using DCM (saturated with ammonia) and MeOH (1%).

Workup

  1. temperatureto warm up to 0 C
  2. temperaturecooled back to −78 C after 15 minutes
  3. additionAfter complete addition
  4. customthe cooling bath is removed
  5. washThe mixture is washed twice with water
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude is purified by chromatography on silicagel

Sources & evidence

ORD record
ord-ef8951e7356c4e998623cca4a3ee2f17
Source dataset
uspto-grants-2012_05
Patent number
US08183366B2

Reaction notes

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