Water → HCID 86649947, compound

HRID 2037467Notes

Reaction equation

HRID 2037467 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][C:12]([C@@H:15]([N:17]2[CH2:22][CH2:21][C@@:20]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)([CH2:23][CH2:24][OH:25])[O:19][C:18]2=[O:33])[CH3:16])=[CH:11][CH:10]=1.CCN(CC)CC.[CH3:41][S:42](Cl)(=[O:44])=[O:43].O>C(Cl)Cl>[CH3:41][S:42]([O:25][CH2:24][CH2:23][C@@:20]1([C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)[O:19][C:18](=[O:33])[N:17]([C@H:15]([C:12]2[CH:13]=[CH:14][C:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])=[CH:10][CH:11]=2)[CH3:16])[CH2:22][CH2:21]1)(=[O:44])=[O:43]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 53361128HCID 53361128, compound

Product 1

HCID 86649947HCID 86649947, compoundYield 98.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (S)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-1,3-oxazinan-2-one (50 mg, 0.11 mmol) in dry CH2Cl2 (2 mL) was added Et3N (33 mg, 0.33 mmol) at 0˜−5° C. Then a solution of MsCl (12 mg, 0.13 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 over, water (10 mL) was added. The layers were separated, and the aqueous layer was extracted with CH2Cl2 (3×10 mL). The combined organic layers was washed with 10% citric acid, aqueous NaHCO3 and brine respectively, dried over Na2SO4, filtered and concentrated to give 2-((S)-3-((S)-1-(2′,4′-difluorobi-phenyl-4-yl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl methanesulfonate (58 mg, crude), which was used for the next step without purification.

Workup

  1. additionAfter addition
  2. additionwas added
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (3×10 mL)
  5. washThe combined organic layers was washed with 10% citric acid, aqueous NaHCO3 and brine respectively
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3d75ffad63594ef7938c63e10c9284ce
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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