tert-butyl (3R)-3-aminopiperidine-1-carboxylate → (3R)-tert-Butyl 3-(1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxamido)piperidine-1-carboxylate

HRID 445267

Reaction equation

HRID 445267 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH2:11][N:10]2[C:19](OC2C=CC([N+]([O-])=O)=CC=2)=[O:20])=[CH:5][CH:4]=1.[C:33]([N:40]1[CH2:45][CH2:44][CH2:43][C@@H:42]([NH2:46])[CH2:41]1)([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34]>CO>[F:31][C:2]([F:1])([F:32])[C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH2:11][N:10]2[C:19]([NH:46][C@@H:42]2[CH2:43][CH2:44][CH2:45][N:40]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:41]2)=[O:20])=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 426351024-Nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 59536392(3R)-tert-Butyl 3-(1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxamido)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 4-nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (350 mg, 0.79 mmol, example 15) and (R)-1-Boc-3-amino-piperidine (1.6 mL, 7.91 mmol) was subjected to a microwave irradiation at 120° C. for 45 min. Then, MeOH (2 mL) was added to the mixture and the mixture was filtered. The solution mixture was purified by preparative HPLC (10%-100% of MeCN (0.1% TFA)/H2O (0.1% TFA). All fractions of the product were combined, saturated NaHCO3 (1 mL) was added and the solvents were removed. Then, an additional amount of saturated NaHCO3 (10 mL) was added and the aqueous mixture was extracted with EtOAc (2×10 mL). The combined organic extracts were dried over MgSO4 and concentrated to give the title compound as a white solid. MS (ESI, positive ion) m/z: 504 (M+H).

Workup

  1. customwas subjected to a microwave irradiation at 120° C. for 45 min
  2. filtrationthe mixture was filtered
  3. customThe solution mixture was purified by preparative HPLC (10%-100% of MeCN (0.1% TFA)/H2O (0.1% TFA)
  4. additionsaturated NaHCO3 (1 mL) was added
  5. customthe solvents were removed
  6. additionThen, an additional amount of saturated NaHCO3 (10 mL) was added
  7. extractionthe aqueous mixture was extracted with EtOAc (2×10 mL)
  8. dry with materialThe combined organic extracts were dried over MgSO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-985b26cf780d4c07b4ad538f7a60e9be
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Linked notes

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