Cesium carbonate → tert-butyl methyl 2-{(1S)-[3-(benzyloxy)phenyl][(tert-butoxycarbonyl)amino]methyl}propanedioate

HRID 526323

Reaction equation

HRID 526323 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])S(C2C=CC=CC=2)(=O)=O)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])(=[O:39])[CH2:34][C:35]([O:37][CH3:38])=[O:36].C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)C1C=C(NC(N[C@@H]2CCCC[C@H]2N(C)C)=S)C=C(C(F)(F)F)C=1>O.C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C@@H:15]([NH:25][C:26]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:32])[CH:34]([C:35]([O:37][CH3:38])=[O:36])[C:33]([O:40][C:41]([CH3:44])([CH3:42])[CH3:43])=[O:39])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 2733872tert-Butyl methyl malonateHCID 114867661-[3,5-Bis(trifluoromethyl)phenyl]-3-[(1R,2R)-(-)-2-(dimethylamino)cyclohexyl]thiourea(R,R-TUC)HCID 71268083HCID 71268083, compound

Product 1

HCID 117653877tert-butyl methyl 2-{(1S)-[3-(benzyloxy)phenyl][(tert-butoxycarbonyl)amino]methyl}propanedioate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Tert-butyl {[3-(benzyloxy)phenyl](phenylsulfonyl)methyl}carbamate (3.0 g, 5.93 mmol) was suspended in a toluene (21.6 mL) water (16 mL) mixture. At 0° C. tert-butyl methyl malonate (1.2 mL, 7.1 mmol), cesium carbonate (1.94 g, 5.9 mmol) and 1-[3,5-bis(trifluoromethy) phenyl]-3-[(1R,2R)-(−)-2-(dimethylamino)cyclohexyl]thiourea (246 mg, 0.59 mmol) was added and the mixture was stirred for 72 hours at 0° C. After storage at −20° C. for 72 hours the mixture was diluted with water and ethyl acetate, after filtration the phases were separated and the aqueous phase extracted with ethyl acetate. The combined extracts were dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (ethyl acetate in hexane 0 to 35%) to yield 2.17 g of enantiomerically enriched tert-butyl methyl 2-{(1S)-[3-(benzyloxy)phenyl][(tert-butoxycarbonyl)amino]methyl}propanedioate.

Workup

  1. filtrationafter filtration the phases
  2. customwere separated
  3. extractionthe aqueous phase extracted with ethyl acetate
  4. dry with materialThe combined extracts were dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel (ethyl acetate in hexane 0 to 35%)

Sources & evidence

ORD record
ord-91abd16de4f848ec89b86b9eb7815cf1
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Linked notes

Loading…