Water → HCID 59201345, compound

HRID 451687Notes

Reaction equation

HRID 451687 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]([O:23][CH2:24][CH2:25][OH:26])[C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]1.CCN(CC)CC.[CH3:34][S:35](Cl)(=[O:37])=[O:36].O>C(Cl)Cl>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]([O:23][CH2:24][CH2:25][O:26][S:35]([CH3:34])(=[O:37])=[O:36])[C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:11]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59201577HCID 59201577, compound

Product 1

HCID 59201345HCID 59201345, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (3R)-tert-butyl 3-((2,3-difluorophenyl)(2-hydroxyethoxy)methyl)piperidine-1-carboxylate in dry CH2Cl2 (50 mL) was added Et3N (5.2 mL, 37.6 mmol) at −5-0° C. Then a solution of MsCl (1.3 g, 11.3 mmol) in dry CH2Cl2 (20 mL) was added dropwise at the same temperature. After addition, the reaction was allowed to gradually warm to rt. Upon completion of the reaction, 50 mL of water was added, the aqueous layer was extracted with CH2Cl2, the combined organic layers were washed with 10% citric acid, sat. NaHCO3 and brine, then dried over Na2SO4, filtered and concentrated to give (3R)-tert-butyl 3-((2,3-difluorophenyl)(2-(methylsulfonyloxy)ethoxy)methyl)piperidine-1-carboxylate (4.2 g, 99%), which was used in the next step without purification. 1H NMR (CDCl3, 400 MHz) δ 7.12 (m, 3H), 4.52 (q, 1H), 4.31 (m, 3H), 4.09 (t, 1H), 3.57 (m, 2H), 3.06 (d, 3H), 2.70 (m, 2H), 1.93 (m, 2H), 1.44 (d, 9H).

Workup

  1. additionAfter addition
  2. additionwas added
  3. extractionthe aqueous layer was extracted with CH2Cl2
  4. washthe combined organic layers were washed with 10% citric acid, sat. NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-0e14c32fd9cf435aa43ce99bc315faba
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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