Triethylamine → HCID 58313132, compound

HRID 1748863Notes

Reaction equation

HRID 1748863 reaction equation
[F:1][C:2]1([F:17])[CH2:16][CH2:15][C:5]2([CH2:9][NH:8][C@H:7]([C:10]([O:12]CC)=[O:11])[CH2:6]2)[CH2:4][CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:42][O:43][C:44]([NH:46][C@H:47]([C:51](O)=[O:52])[CH:48]([CH3:50])[CH3:49])=[O:45].C(N(CC)CC)C>C(Cl)Cl>[F:17][C:2]1([F:1])[CH2:3][CH2:4][C:5]2([CH2:9][N:8]([C:51](=[O:52])[C@H:47]([CH:48]([CH3:49])[CH3:50])[NH:46][C:44]([O:43][CH3:42])=[O:45])[C@H:7]([C:10]([OH:12])=[O:11])[CH2:6]2)[CH2:15][CH2:16]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 58313096HCID 58313096, compound

Product 1

HCID 58313132HCID 58313132, compoundYield 93.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl (3S)-8,8-difluoro-2-azaspiro[4.5]decane-3-carboxylate (115), (380 mg, 1.54 mmol) in anhydrous CH2Cl2 (10 mL) was added HATU (614 mg, 1.6 mmol), N-[(methyloxy)carbonyl]-L-valine (283 mg, 1.6 mmol) followed by triethylamine (0.43 mL, 3.1 mmol) and the reaction stirred at room temperature under nitrogen for 1 h. The reaction was concentrated in vacuo and the residue purified by silica gel chromatography eluting with 15-80% hexanes/EtOAc. Appropriate fractions were combined and concentrated in vacuo. The residue was dissolved in THF/water/methanol (5 mL/2.5 mL/2.5 mL) and lithium hydroxide monohydrate was added (119 mg, 2.8 mmol) and the solution stirred at room temperature for 30 min. The reaction was treated with 1N HCl (3.5 mL) and partitioned between EtOAc and water (50 mL each). The aqueous layer was extracted with ethyl acetate (50 mL), the organic layers were combined and dried (MgSO4) and concentrated in vacuo. The residue was triturated in diethyl ether and concentrated in vacuo to afford the title compound as a white solid (542 mg, 93% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.47 (br. s., 1H) 7.41 (d, J=8.0 Hz, 1H) 4.24 (t, J=8.6 Hz, 1H) 3.95-4.14 (m, 2H) 3.52 (s, 3H) 3.25-3.33 (m, 1H) 2.22 (dd, J=12.3, 8.4 Hz, 1H) 1.79-2.11 (m, 5H) 1.58-1.77 (m, 3H) 1.41-1.59 (m, 2H) 0.93 (dd, J=12.7, 6.6 Hz, 6H). LC-MS ESI (M+H)+=377.23.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customthe residue purified by silica gel chromatography
  3. washeluting with 15-80% hexanes/EtOAc
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in THF/water/methanol (5 mL/2.5 mL/2.5 mL)
  6. additionlithium hydroxide monohydrate was added (119 mg, 2.8 mmol)
  7. stirringthe solution stirred at room temperature for 30 min
  8. additionThe reaction was treated with 1N HCl (3.5 mL)
  9. custompartitioned between EtOAc and water (50 mL each)
  10. extractionThe aqueous layer was extracted with ethyl acetate (50 mL)
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated in vacuo
  13. customThe residue was triturated in diethyl ether
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4620ad24d647401fbb0d3c2072eadf8c
Source dataset
uspto-grants-2015_10
Patent number
US09150587B2

Reaction notes

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