Acetic Acid → HCID 24905914, compound

HRID 1768474Notes

Reaction equation

HRID 1768474 reaction equation
[Si]([O:8][CH2:9][C:10]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:14]=[C:13]([C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[F:22])[CH2:12][N:11]1[C:23]([N:25]([CH3:32])[CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)=[O:24])(C(C)(C)C)(C)C.CC(O)=O.C(O[C:46]1(O[Si](C)(C)C)[CH2:48][CH2:47]1)C.[BH3-]C#N.[Na+].FC(F)(F)C(O)=O>CO>[CH:46]1([N:29]2[CH2:28][CH2:27][CH:26]([N:25]([CH3:32])[C:23]([N:11]3[CH2:12][C:13]([C:15]4[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=4[F:22])=[CH:14][C@@:10]3([CH2:9][OH:8])[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:24])[CH2:31][CH2:30]2)[CH2:48][CH2:47]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 10098834HCID 10098834, compound

Product 1

HCID 24905914HCID 24905914, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

To 30 mg (0.055 mmol) of amine 7-2 in MeOH was added 30 μL (0.55 mmol) of HOAc, 33 μL (0.17 mmol) of (1-ethoxycyclopropoxy)trimethylsilane, 10 mg (0.17 mmol) of NaCNBH3 and 100 mg of 4 Å molecular sieves. The mixture was then heated at 100° C. for 10 min in a microwave reactor. After cooling to room temperature, ˜500 μL of trifluoroacetic acid was added and the mixture was stirred for 1 h. The reaction was partitioned between EtOAc and saturated NaHCO3, the layers were separated, the organic phase was washed with water, brine, dried over MgSO4, and concentrated by rotary evaporation. The residue was purified by column chromatography on silica gel with 20:1:1 EtOH/NH4OH/H2O in EtOAc to provide 15-1 as a white solid. Data for 15-1: 1HNMR (500 MHz, CDCl3) δ 7.4-7.2 (m, 5H), 7.1-6.9 (m, 3H), 6.3 (s, 1H), 5.45 (m, 1H), 4.8 (m, 1H), 4.6 (m, 1H), 4.4 (m, 1H), 4.0 (m, 1H), 3.75 (m, 1H), 3.15 (m, 2H), 2.9 (s, 3H), 2.3 (m, 2H), 1.9-1.6 (m, 5H), 0.5-0.4 (m, 4H) ppm. HRMS (ES) calc'd M+H for C27H31F2N3O2: 468.2457. Found: 468.2438. Resolution of the enantiomers was carried out chromatographically using a Chiralpak AD© 10×50 cm column with 15% isopropanol in hexanes (with 0.1% diethylamine) at 150 mL/min. Analytical HPLC analysis of the eluent on a 4×250 mm Chiralpak AD® column with 15% isopropanol in hexanes (with 0.1% diethylamine) at 1 mL/min indicated that inactive enantiomer has Rt=7.05 min and the active enantiomer has Rt=8.17 min.

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe reaction was partitioned between EtOAc and saturated NaHCO3
  3. customthe layers were separated
  4. washthe organic phase was washed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated by rotary evaporation
  7. customThe residue was purified by column chromatography on silica gel with 20:1:1 EtOH/NH4OH/H2O in EtOAc

Sources & evidence

ORD record
ord-d443428118ec42868ab8c7762ce627b9
Source dataset
uspto-grants-2007_06
Patent number
US07235580B2

Reaction notes

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