tert-Butanol → HCID 68615095, compound

HRID 859217Notes

Reaction equation

HRID 859217 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([N:14]3[C:18](=[O:19])[CH2:17][CH:16](C(O)=O)[CH2:15]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C[N:26]1[CH2:31]COCC1.ClC(OCC(C)C)=[O:34].[N-]=[N+]=[N-].[Na+].[C:44]([OH:48])([CH3:47])([CH3:46])[CH3:45]>O1CCCC1.O.C1(C)C=CC=CC=1>[C:44]([O:48][C:31](=[O:34])[NH:26][CH:16]1[CH2:17][C:18](=[O:19])[N:14]([C:11]2[CH:12]=[CH:13][C:8]([O:7][CH2:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:24][CH:23]=3)=[CH:9][CH:10]=2)[CH2:15]1)([CH3:47])([CH3:46])[CH3:45]

Participants

9

Reactant 5

HCID 6386tert-ButanolHCID 79724-MethylmorpholineHCID 33557Sodium AzideHCID 62365Isobutyl chloroformateHCID 17608004HCID 17608004, compound

Product 1

HCID 68615095HCID 68615095, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

A solution of 5.16 g (15.7 mmol) of (RS)-1-[4-(4-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid in 70 ml of tetrahydrofurane is treated with 1.76 ml (15.7 mmol) of N-methylmorpholine. Thereafter, the reaction mixture is cooled to −10° C. and 2.08 ml (15.7 mmol) of isobutyl chloroformate are added. After stirring for 3 min, a solution of 2.06 g (31.3 mmol) of sodium azide in 10 ml of water are added while the temperature rises to 0° C. After stirring for 45 min at 0° C., the suspension is diluted with 200 ml toluene and transferred into a separatory funnel. The organic layer is washed twice with 1000 ml of a saturated solution of sodium hydrogencarbonate and twice with 100 ml of a saturated solution of sodium chloride. Thereafter, the organic layer is dried over sodium sulfate and the solvent is evaporated to end with a volume of about 80 ml. The solution is heated gradually to 80° C. and kept at this temperature for 30 min. Thereafter, 35.3 ml (376 mmol) of tert-butanol are added and the mixture is stirred at 80° C. for 18 hours. Then the solvent is removed under reduced pressure, and the residue is chromatographed on silica gel using a 98:2-mixture of dichloromethane and methanol as the eluent. There are obtained 4.82 g (77% of theory) of (RS)-{1-[4-(4-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidin-3-yl}-carbamic acid tert-butyl ester as a white solid. MS: m/e=401 (M+H)+.

Workup

  1. customrises to 0° C
  2. stirringAfter stirring for 45 min at 0° C.
  3. customtransferred into a separatory funnel
  4. washThe organic layer is washed twice with 1000 ml of a saturated solution of sodium hydrogencarbonate and twice with 100 ml of a saturated solution of sodium chloride
  5. dry with materialThereafter, the organic layer is dried over sodium sulfate
  6. customthe solvent is evaporated
  7. temperatureThe solution is heated gradually to 80° C.
  8. waitkept at this temperature for 30 min
  9. stirringthe mixture is stirred at 80° C. for 18 hours
  10. customThen the solvent is removed under reduced pressure
  11. customthe residue is chromatographed on silica gel using a 98

Sources & evidence

ORD record
ord-e74d2d29dc264d1a89f92cbddf218fce
Source dataset
uspto-grants-2006_12
Patent number
US07151111B2

Reaction notes

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