Triethylamine → HCID 88924281, compound

HRID 712957Notes

Reaction equation

HRID 712957 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:25][CH2:24][C:11]2([O:16][CH:15]([C:17](O)=[O:18])[CH2:14][N:13]([CH2:20][CH:21]([F:23])[F:22])[CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:26][CH2:27][C:28](=[O:31])[CH2:29][CH3:30].C(N(CC)CC)C>CC1CCCO1>[F:22][CH:21]([F:23])[CH2:20][N:13]1[CH2:12][C:11]2([CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:25][CH2:24]2)[O:16][CH:15]([C:17](=[O:18])[NH:26][CH2:27][C:28](=[O:31])[CH2:29][CH3:30])[CH2:14]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 116079131-aminobutan-2-oneHCID 86672461HCID 86672461, compound

Product 1

HCID 88924281HCID 88924281, compoundYield 60.2%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To 9-(tert-butoxycarbonyl)-4-(2,2-difluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-2-carboxylic acid (418 mg, 1.15 mmol), 1-aminobutan-2-one (156 mg, 1.26 mmol) and propane phosphonic acid anhydride (T3P) (1.095 g, 1.0 mL of 50% w/w, 1.72 mmol) in 2-methyltetrahydrofuran (3.1 mL) was added triethylamine (640 μL, 4.59 mmol) at room temperature. The reaction mixture was then heated at 40° C. for 5 hours. The reaction mixture was cooled quenched with sat. aq. NaHCO3 and extracted with ethyl acetate. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo, then purified by silica gel column chromatography using 0-50% EtOAc in DCM to yield tert-butyl 4-(2,2-difluoroethyl)-2-((2-oxobutyl)carbamoyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (300 mg, 60%). 1H NMR (400 MHz, CDCl3) δ 7.40-7.30 (m, 1H), 6.09-5.64 (m, 1H), 4.31 (dd, J=11.0, 3.0 Hz, 1H), 4.21-4.05 (m, 2H), 3.77 (ddt, J=10.9, 7.5, 6.3 Hz, 2H), 3.39-3.17 (m, 2H), 3.14-2.95 (m, 1H), 2.80-2.63 (m, 3H), 2.50 (q, J=7.3 Hz, 2H), 2.41-2.27 (m, 1H), 2.25-2.11 (m, 2H), 1.67-1.51 (m, 3H), 1.46 (s, 9H), 1.13 (t, J=7.4 Hz, 3H). ESI-MS m/z calc. 433.2. found 434.5 (M+1)+; Retention time: 1.78 minutes (3 min run).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customquenched with sat. aq. NaHCO3
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-565f2fb68c1d4509ba40cfec9ce7f7a9
Source dataset
uspto-grants-2015_11
Patent number
US09181273B2

Reaction notes

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