Water → HCID 59598527, compound

HRID 2266287Notes

Reaction equation

HRID 2266287 reaction equation
[F:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[CH:9]=2)=[C:6]([C@H:15]([O:29][CH2:30][CH2:31][OH:32])[C@@H:16]2[O:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]2)[CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:40][S:41](Cl)(=[O:43])=[O:42].O>C(Cl)Cl>[F:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[CH:9]=2)=[C:6]([C@H:15]([O:29][CH2:30][CH2:31][O:32][S:41]([CH3:40])(=[O:43])=[O:42])[C@@H:16]2[O:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:17]2)[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59598494HCID 59598494, compound

Product 1

HCID 59598527HCID 59598527, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-tert-butyl 2-((S)-(6-fluoro-3′-methylbiphenyl-2-yl)(2-hydroxyethoxy)methyl)morpholine-4-carboxylate (498 mg, 1.12 mmol) in dry CH2Cl2 (15 mL) was added Et3N (472 mg, 4.68 mmol) at ˜0 to −5° C. A solution of MsCl (267 mg, 2.34 mmol) in dry CH2Cl2 (10 mL) was added dropwise at the same temperature. The mixture was allowed to warm to rt gradually. Tlc showed the stating material had disappeared. Water (10 mL) was added and the aqueous layer was extracted with CH2Cl2 (3×20 mL). The combined organic layers were washed with 10% aq citric acid, satd aq NaHCO3 and brine, dried over Na2SO4, filtered and concentrated to afford crude (R)-tert-butyl 2-((S)-(6-fluoro-3′-methylbiphenyl-2-yl)(2-(methylsulfonyloxy)ethoxy)methyl)morpholine-4-carboxylate (554 mg, 95%). which was used in the next step without further purification. MS (E/Z): 524 (M+H+)

Workup

  1. extractionthe aqueous layer was extracted with CH2Cl2 (3×20 mL)
  2. washThe combined organic layers were washed with 10% aq citric acid
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-171d97e4381546fc846ad3a34cd66be8
Source dataset
uspto-grants-2010_12
Patent number
US07858624B2

Reaction notes

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