Sodium Methoxide → HCID 68613216, compound

HRID 2095294Notes

Reaction equation

HRID 2095294 reaction equation
C([O:6][CH2:7][C@H:8]1[CH2:10][C@@H:9]1[C:11]1[CH:12]=[N:13][CH:14]=[C:15]([O:17][CH2:18][C@@H:19]2[CH2:22][CH2:21][N:20]2[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:16]=1)(=O)C(C)C.C[O-].[Na+]>CO>[C:26]([O:25][C:23]([N:20]1[CH2:21][CH2:22][C@H:19]1[CH2:18][O:17][C:15]1[CH:16]=[C:11]([C@H:9]2[CH2:10][C@@H:8]2[CH2:7][OH:6])[CH:12]=[N:13][CH:14]=1)=[O:24])([CH3:29])([CH3:28])[CH3:27]

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 68611371HCID 68611371, compound

Product 1

HCID 68613216HCID 68613216, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of (1S,2S)-2-[5-[[1-(tert-butoxycarbonyl)-(2S)-azetidinyl]methoxy]-3-pyridyl]cyclopropylmethyl isobutyrate (2.82 g, 6.97 mmol) in anhydrous methanol (35 mL) in a 250 mL round-bottom flask with magnetic stirrer was added a 25-30 wt % solution of sodium methoxide in methanol (0.4 mL; d 0.97 kg/L according to supplier, which makes approx. 2 mmol). The flask was fitted with an Ar balloon, the atmosphere was exchanged, and the reaction mixture was kept at 40° C. for 6 h. The reaction mixture was evaporated and the residue directly filtered over silica gel (24×3.8 cm, CH2Cl2/MeOH 93:7, then 9:1). Evaporation and drying (50° C./oil pump) gave 2.29 g (98%) of a slightly yellowish glass. 1H NMR (CDCl3, TMS, 400 MHz) δ 8.13 (d, 1H, J=2.8 Hz), 8.04 (narrow m, 1H), 6.89 (m, 1H), 4.50 (m, 1H), 4.29 (m, 1H), 4.12 (m, 1H; the main structure of this signal is a dd with J=2.8 and 10.1 Hz, accompanied by minor peaks that may result from the presence of a second rotamer), 3.93-3.85 (m, 2H), 3.68, 3.62 (ABq, 2H, J=11.4 Hz, low-field part d with J=6.4 Hz, high-field part d with J=6.9 Hz), 2.40-2.22 (m, 2H), 1.83 (m, 1H), 1.70 (very br, 1H, OH), 1.48 (m, 1H), 1.42 (s, 9H), 1.03-0.97 (m, 2H). MS (EI) m/z 334 (M+, 1.0%), 278 (M+-C4H8, 2.4%), 237 (10%), 178 (19%), 100 (21%), 57 (100%), 56 (76%), 41 (44%).

Workup

  1. customThe flask was fitted with an Ar balloon
  2. customThe reaction mixture was evaporated
  3. filtrationthe residue directly filtered over silica gel (24×3.8 cm, CH2Cl2/MeOH 93:7
  4. customEvaporation
  5. customdrying (50° C./oil pump)
  6. customgave 2.29 g (98%) of a slightly yellowish glass

Sources & evidence

ORD record
ord-739f1f4c3b5c444eaa0645089f0ddc1a
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

Loading…