Water → HCID 59396006, compound

HRID 1094752Notes

Reaction equation

HRID 1094752 reaction equation
CC([Si](C1C=CC=CC=1)(C1C=CC=CC=1)[O:6][CH2:7][C@@H:8]1[CH2:14][C@H:13]2[C@H:11]([CH2:12]2)[CH2:10][N:9]1[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])(C)C.C1C=CN=CC=1.F.O.CCOC(C)=O>N1C=CC=CC=1>[OH:6][CH2:7][C@@H:8]1[CH2:14][C@H:13]2[C@H:11]([CH2:12]2)[CH2:10][N:9]1[C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16]

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 64774Pyridine, hydrofluoride (1:1)HCID 59396023HCID 59396023, compound

Product 1

HCID 59396006HCID 59396006, compoundYield 91.9%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To an ice cooled solution of phenylmethyl (1S,4S,6S)-4-({[(1,1-dimethylethyl)(diphenyl)silyl]oxy}methyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate D8 (0.930 g) in pyridine (14 ml) was added HF-pyridine (2.642 ml, 30.4 mmol), the resulting mixture was stirred for 20 minutes at 0° C. and then was slowly warmed to room temperature and stirred for 30 minutes. Water (200 ml) and EtOAc (30 ml) were added and stirred for 15 minutes. The organic phase was separated and the aqueous phase was extracted with EtOAc (6×5 mls). The collected organic layers were dried (Na2SO4), filtered and evaporated under reduced pressure to obtain an oil which was purified via Companion CombiFlash (Silica gel, SNAP 100 g column; eluted with 20 CV of DCM/MeOH 98/2). Collected and evaporated fractions gave the title compound D9 (0.447 g). MS: (ES/+) m/z: 262 (M+1). C15H19NO3 requires 261. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.51-7.24 (m, 5 H), 5.20-5.0 (m, 2 H), 4.73-4.48 (m, 1 H), 4.43-4.17 (m, 1 H), 3.71-3.51 (m, 1 H), 3.51-2.35 (m, 2 H), 2.46-2.24 (m, 2 H), 1.20-0.95 (m, 2 H), 0.95-0.59 (m, 2 H), 0.21-0.09 (m, 1 H).

Workup

  1. temperaturewas slowly warmed to room temperature
  2. stirringstirred for 30 minutes
  3. stirringstirred for 15 minutes
  4. customThe organic phase was separated
  5. extractionthe aqueous phase was extracted with EtOAc (6×5 mls)
  6. dry with materialThe collected organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto obtain an oil which
  10. customwas purified via Companion CombiFlash (Silica gel, SNAP 100 g column; eluted with 20 CV of DCM/MeOH 98/2)
  11. customCollected
  12. customevaporated fractions

Sources & evidence

ORD record
ord-750e3553103f4ad383dd7bd2faa39437
Source dataset
uspto-grants-2012_03
Patent number
US08133908B2

Reaction notes

Loading…