Water → HCID 58109301, compound

HRID 2037559Notes

Reaction equation

HRID 2037559 reaction equation
[CH2:1]([C@@:4]1([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH:20]([F:22])[F:21])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].[OH2:30]>C1COCC1.C(Cl)Cl>[F:21][CH:20]([F:22])[O:19][C:16]1[CH:17]=[CH:18][C:13]([C@@H:11]([N:7]2[CH2:6][CH2:5][C@@:4]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)([CH2:1][CH2:2][CH2:3][OH:30])[O:9][C:8]2=[O:10])[CH3:12])=[CH:14][CH:15]=1

Participants

5

Reactant 2

HCID 962WaterHCID 58109243HCID 58109243, compound

Product 1

HCID 58109301HCID 58109301, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-9 °C

Procedure

A solution of (R)-6-allyl-3-((S)-1-(4-(difluoromethoxy)phenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (0.2780 g, 0.686 mmol, 1.0 equiv) in THF (20 mL) was degassed and then cooled with an ice-salt bath (−9° C.). To this solution was added a solution of 1.0 M BH3.THF complex in THF (1.5 mL, 1.5 mmol, 2.2 equiv). The resulting mixture was allowed to slowly warm to rt while stirring overnight (21 h) and then quenched with H2O (3 mL) and NaBO3.H2O (0.680 g, 6.8 mmol, 10 equiv). The mixture was vigorously stirred at rt overnight and then diluted with CH2Cl2, and dried over Na2SO4. After the solvents were evaporated, the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate to give 0.2337 g (80%) of (R)-3-((S)-1-(4-(difluoromethoxy)phenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one. LC-MS Method 1 tR=1.59 min, m/z 446 (MNa+), 380, 210, 171; 1H NMR (400 MHz, CD3OD) δ 7.27-7.23 (m, 2H), 7.04 (t, J=8.8 Hz, 2H), 6.94 (d, J=8.5 Hz, 2H), 6.85 (d, J=8.8 Hz, 2H), 6.67 (t, J=74.1 Hz, 1H), 5.48 (q, J=7.1 Hz, 1H), 3.43-3.39 (m, 2H), 3.07-3.02 (m, 1H), 2.42-2.37 (m, 1H), 2.26-2.10 (m, 2H), 1.91-1.85 (m, 2H), 1.58-1.50 (m, 1H), 1.46 (d, J=7.0 Hz, 3H), 1.29-1.20 (m, 1H); 19F NMR (376 MHz, CD3OD) δ −83.95 (d, J=73.8 Hz), −117.51 (m).

Workup

  1. temperatureto slowly warm to rt
  2. stirringThe mixture was vigorously stirred at rt overnight
  3. dry with materialdried over Na2SO4
  4. customAfter the solvents were evaporated
  5. customthe residue was purified by chromatography on silica gel
  6. washeluted with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-9439b5609d334295b2e1d63dbd29e709
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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