Water → HCID 86626185, compound

HRID 2355326Notes

Reaction equation

HRID 2355326 reaction equation
[F:1][C:2]1([F:20])[CH2:7][CH2:6][CH:5]([CH2:8][C@H:9]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:10][OH:11])[CH2:4][CH2:3]1.CCN(CC)CC.[CH3:28][S:29](Cl)(=[O:31])=[O:30].[OH2:33]>C(Cl)Cl>[C:15]([O:14][C:13]([NH:12][C@@H:9]([CH2:8][CH:5]1[CH2:6][CH2:7][C:2]([F:20])([F:1])[CH2:3][CH2:4]1)[CH2:10][CH2:28][S:29]([OH:31])(=[O:33])=[O:30])=[O:19])([CH3:18])([CH3:17])[CH3:16].[CH3:28][S:29]([OH:31])(=[O:11])=[O:30]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59383050HCID 59383050, compound

Product 1

HCID 86626185HCID 86626185, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (S)-tert-butyl 1-(4,4-difluorocyclohexyl)-3-hydroxypropan-2-ylcarbamate (25.7 g, 0.088 mol) in dry CH2Cl2 (300 mL) was added Et3N (35.4 g, 46.2 mL) at 0 to −5° C. A solution of methanesulfonyl chloride (20.1 g, 0.1754 mol) in dry CH2Cl2 (150 mL) was added dropwise at the same temperature. After addition, the mixture was allowed to warm to rt gradually. 300 mL of water was added and the aqueous layer was extracted with CH2Cl2 (3×100 mL). The combined organic layers were washed with 10% aq citric acid, satd aq NaHCO3 and brine, dried over Na2SO4, filtered and concentrated to give methanesulfonic acid (S)-2-(tert-butoxycarbonylamino)-3-(4,4-difluorocyclohexyl)propyl methanesulfonate (28.8 g, 89%), which was used in the next step without purification. 1H NMR (400 MHz, CDCl3): 4.57 (d, J=6.8 Hz, 1H), 4.27 (m, 1H), 4.16 (m, 1H), 3.97 (m, 1H), 3.03 (s, 3H), 2.40-1.20 (m, 11H), 1.44 (s, 9H); MS (E/Z): 372 (M+H+).

Workup

  1. additionAfter addition
  2. extractionthe aqueous layer was extracted with CH2Cl2 (3×100 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-074ff121497a472fb9b5a34db55bbe31
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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