Isopropanol → HCID 71278253, compound

HRID 1427396Notes

Reaction equation

HRID 1427396 reaction equation
[Na].CS([O:6][CH2:7][C@@H:8]1[O:25][CH2:24][C@:11]2([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[F:32])[N:12]=[C:13]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[S:14][CH2:15][C@@H:10]2[CH2:9]1)(=O)=O.[Cl-].[NH4+].[CH3:35][CH:36](O)[CH3:37]>>[F:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C@:11]12[CH2:24][O:25][C@@H:8]([CH2:7][O:6][CH:36]([CH3:37])[CH3:35])[CH2:9][C@H:10]1[CH2:15][S:14][C:13]([NH:16][C:17](=[O:18])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[N:12]2

Participants

5

Reactant 4

HCID 3776Isopropanol3×HCID 25517Ammonium ChlorideHCID 5360545Sodium2×HCID 86677105HCID 86677105, compound

Product 1

HCID 71278253HCID 71278253, compound

Procedure

The sodium salt of 2-propanol (34 mg, 0.41 mmol) was dissolved in 2-propanol (1.5 mL), and this was added to a solution of [(4aR,6R,8aS)-2-[(tert-butoxycarbonyl)amino]-8a-(2-fluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-6-yl]methyl methanesulfonate (C19) (40 mg, 0.084 mmol) in 2-propanol (0.5 mL). After 18 hours, additional sodium salt (34 mg, 0.41 mmol) was added, and stirring was continued for 66 hours. After addition of aqueous ammonium chloride solution, the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with water, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification was carried out via preparative thin layer chromatography on silica gel (Eluent: 1:1 ethyl acetate/heptane) to provide the product as a white foam. Yield: 11.2 mg, 0.255 mmol, 30%. LCMS m/z 439.4 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.19 (br d, J=6.2 Hz, 6H), 1.54 (s, 9H), 1.63-1.71 (br m, 1H), 1.83-1.97 (br m, 1H), 2.50-2.59 (m, 1H), 2.93 (dd, J=13, 4 Hz, 1H), 3.07-3.18 (br m, 1H), 3.41 (dd, J=9.9, 4.8 Hz, 1H), 3.58-3.68 (m, 2H), 3.72-3.89 (m, 2H), 4.20 (br d, J=12 Hz, 1H), 7.05-7.12 (m, 1H), 7.17-7.23 (m, 1H), 7.30-7.40 (m, 2H).

Workup

  1. waitwas continued for 66 hours
  2. extractionthe mixture was extracted three times with ethyl acetate
  3. washThe combined organic layers were washed with water
  4. washwashed with saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification

Sources & evidence

ORD record
ord-1c1ffdcb3dc043d59817c38024058c8d
Source dataset
uspto-grants-2015_01
Patent number
US08933221B2

Reaction notes

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