Water → HCID 59532363, compound

HRID 2193455Notes

Reaction equation

HRID 2193455 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N:15]2[CH2:20][CH2:19][C:18]([CH2:27][CH2:28][OH:29])([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:17][C:16]2=[O:30])[CH:10]=1.CCN(CC)CC.[CH3:38][S:39](Cl)(=[O:41])=[O:40].O>C(Cl)Cl>[CH3:38][S:39]([O:29][CH2:28][CH2:27][C:18]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:17][C:16](=[O:30])[N:15]([C:11]2[CH:10]=[C:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[CH:14]=[CH:13][CH:12]=2)[CH2:20][CH2:19]1)(=[O:41])=[O:40]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 25182275HCID 25182275, compound

Product 1

HCID 59532363HCID 59532363, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-(2′,4′-difluorobiphenyl-3-yl)-6-(2-hydroxyethyl)-6-phenyl-1,3-oxazinan-2-one (200 mg, 0.49 mmol) in dry CH2Cl2 (4 mL) was added Et3N (0.234 mL, 1.46 mmol) at 0˜−5° C. A solution of methanesulfonyl chloride (67 mg, 0.59 mmol) in dry CH2Cl2 (1 mL) was added dropwise at the same temperature. After addition, the mixture was allowed to warm to rt gradually. When the reaction was complete, water (10 mL) was added and the mixture was extracted with CH2Cl2 (3×10 mL). The combined organic layers were washed with 10% aq citric acid, satd aq NaHCO3 and brine, then dried over Na2SO4, filtered and concentrated to give 2-(3-(2′,4′-difluorobiphenyl-3-yl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)ethyl methanesulfonate (230 mg, 97%), which was used in the next step without purification.

Workup

  1. additionAfter addition
  2. extractionthe mixture was extracted with CH2Cl2 (3×10 mL)
  3. washThe combined organic layers were washed with 10% aq citric acid
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-4bb6c28edc484e3bb17f18b1380e4504
Source dataset
uspto-grants-2012_12
Patent number
US08329897B2

Reaction notes

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