Triethylamine → Tert-butyl 10-(acetonylcarbamoyl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72880Notes

Reaction equation

HRID 72880 reaction equation
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[C:19]([O:23][C:24]([N:26]1[CH2:44][CH2:43][C:29]2([O:34][CH:33]([C:35](O)=[O:36])[CH2:32][N:31]([CH2:38][C:39]([F:42])([F:41])[F:40])[CH2:30]2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].Cl.[NH2:46][CH2:47][C:48](=[O:50])[CH3:49].CCN(CC)CC>CC1CCCO1>[CH2:47]([NH:46][C:35]([CH:33]1[O:34][C:29]2([CH2:43][CH2:44][N:26]([C:24]([O:23][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:25])[CH2:27][CH2:28]2)[CH2:30][N:31]([CH2:38][C:39]([F:41])([F:40])[F:42])[CH2:32]1)=[O:36])[C:48]([CH3:49])=[O:50]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 30840252-Propanone, 1-amino-, hydrochlorideHCID 682914539-(Tert-butoxycarbonyl)-4-(2,2,2-trifluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-2-carboxylic acid

Product 1

HCID 70872681Tert-butyl 10-(acetonylcarbamoyl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateYield 49.4%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

T3P (591 mg, 553 μL of 50% w/w, 0.93 mmol) was added to a mixture of 9-(tert-butoxycarbonyl)-4-(2,2,2-trifluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-2-carboxylic acid (142 mg, 0.37 mmol), 1-aminopropan-2-one hydrochloride salt (41 mg, 0.37 mmol) and Et3N (188 mg, 259 μL, 1.86 mmol) in 2-methyltetrahydrofuran (706 μL). The reaction mixture was then heated at 45° C. for 2 hours. The reaction mixture was cooled to room temperature and partitioned between EtOAc/saturated aq. NaHCO3. The layers were separated and the aqueous layer was extracted with EtOAc (2×). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to a dark foam. The crude product was purified by silica gel column chromatography using 0-50% EtOAC in DCM as eluent to afford tert-butyl 10-(acetonylcarbamoyl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (80 mg, 49%) as a yellow solid. ESI-MS m/z calc. 437.5. Found 438.7 (M+1)+; Retention time: 1.01 minutes (3 min run).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc/saturated aq. NaHCO3
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×)
  5. dry with materialThe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to a dark foam
  8. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e5a8afaf5bea4892a985b8c7ef9c8c87
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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