Triethylamine → HCID 67979956, compound

HRID 1622304Notes

Reaction equation

HRID 1622304 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH3:17])([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH2:41]1[C:50]2[C:45](=[CH:46][C:47]([C:51]([O:53][CH3:54])=[O:52])=[CH:48][CH:49]=2)[CH2:44][CH2:43][NH:42]1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([C:14]([N:42]2[CH2:43][CH2:44][C:45]3[C:50](=[CH:49][CH:48]=[C:47]([C:51]([O:53][CH3:54])=[O:52])[CH:46]=3)[CH2:41]2)=[O:16])([CH3:17])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 232828481-[(Tert-butoxy)carbonyl]-4-methylpiperidine-4-carboxylic acidHCID 42614607Methyl 1,2,3,4-tetrahydroisoquinoline-6-carboxylate hydrochloride

Product 1

HCID 67979956HCID 67979956, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1-(tert-butoxycarbonyl)-4-methylpiperidine-4-carboxylic acid (0.830 g, 3.41 mmol) and triethylamine (0.792 mL, 5.68 mmol) in DMF (11.0 mL) was treated with TFFH (1.13 g, 4.26 mmol). The resulting mixture was stirred at rt for 30 min and then methyl 1,2,3,4-tetrahydroisoquinoline-6-carboxylate hydrochloride (0.647 g, 2.84 mmol) and triethylamine (0.792 mL, 5.68 mmol) were added. The reaction mixture was stirred at rt for 2 days and then extracted with EtOAc three times. The combined organic phases were washed with water and brine, dried over Na2SO4, filtered and concentrated. Purification of the resulting residue by column chromatography (SiO2, 0-100% EtOAc in hexane) provided methyl 2-{[1-(tert-butoxycarbonyl)-4-methylpiperidin-4-yl]carbonyl}-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (0.959 g, 82%). LC-MS: (FA) ES+ 439 (M+Na); 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J=10.1, 2.2 Hz, 2H), 7.19 (d, J=8.0 Hz, 1H), 4.79 (s, 2H), 3.95-3.77 (m, 5H), 3.67 (d, J=38.1 Hz, 2H), 3.21 (s, 2H), 2.92 (t, J=5.7 Hz, 2H), 2.24-2.10 (m, 2H), 1.61 (d, J=10.8 Hz, 1H), 1.44 (d, J=5.0 Hz, 10H), 1.33 (d, J=3.6 Hz, 3H).

Workup

  1. stirringThe reaction mixture was stirred at rt for 2 days
  2. extractionextracted with EtOAc three times
  3. washThe combined organic phases were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the resulting residue by column chromatography (SiO2, 0-100% EtOAc in hexane)

Sources & evidence

ORD record
ord-efe5648b45ae4e7e82d391a52217d12f
Source dataset
uspto-grants-2014_07
Patent number
US08778931B2

Reaction notes

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