2,6-Lutidine → HCID 86635705, compound

HRID 552786Notes

Reaction equation

HRID 552786 reaction equation
[Cl:1][C:2]1[C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=[C:4]([CH2:11][C@H:12]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C@H:13]([OH:19])[C:14]2[S:15][CH:16]=[CH:17][N:18]=2)[CH:3]=1.N1C(C)=CC=CC=1C.O([Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])S(C(F)(F)F)(=O)=O.CCN(C(C)C)C(C)C.C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C.C1COCC1>C(Cl)Cl>[Si:44]([O:19][C@H:13]([C:14]1[S:15][CH:16]=[CH:17][N:18]=1)[C@@H:12]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:26])[CH3:25])[CH2:11][C:4]1[CH:3]=[C:2]([Cl:1])[C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45]

Participants

8

Reactant 6

HCID 79372,6-LutidineHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 86635704HCID 86635704, compound

Product 1

HCID 86635705HCID 86635705, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of tert-butyl (1S,2S)-3-(7-chlorobenzo[d][1,3]dioxol-5-yl)-1-hydroxy-1-(thiazol-2-yl)propan-2-ylcarbamate (3.250 g, 8 mmol) in DCM (24 mL) was treated with 2,6-lutidine (1 ml, 12 mmol) followed by tert-butyldimethylsilyl triflate (2 ml, 9 mmol) and was allowed to stir at RT for 2 hours. An additional equivalent of TBS triflate was added followed by an additional equivalent of base. After 1 hour, DIEA (2 ml, 12 mmol) was added, followed by di-tert-butyldicarbonate 1M in THF (8 ml, 8 mmol), and the reaction mixture was allowed to stir at RT overnight. The reaction mixture was quenched with 2N HCl solution, diluted with DCM, and washed with saturated NaHCO3 solution and brine. The organics were dried over MgSO4 and concentrated under reduced pressure. Purification of the crude residue by column chromatography gave tert-butyl (1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(7-chlorobenzo[d][1,3]dioxol-5-yl)-1-(thiazol-2-yl)propan-2-ylcarbamate (1.850 g, 45% yield).

Workup

  1. waitAfter 1 hour
  2. stirringto stir at RT overnight
  3. customThe reaction mixture was quenched with 2N HCl solution
  4. additiondiluted with DCM
  5. washwashed with saturated NaHCO3 solution and brine
  6. dry with materialThe organics were dried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customPurification of the crude residue by column chromatography

Sources & evidence

ORD record
ord-80c65c2d825b4c61bb0ce21e8bf1aa18
Source dataset
uspto-grants-2011_05
Patent number
US07951838B2

Reaction notes

Loading…