Water → 1-((2S,4R)-1-(tert-butyldimethylsilyloxy)-4,5-dihydroxypentan-2-yl)-3-(2-chloro-3-fluorobenzyl)-1-methylurea

HRID 340985Notes

Reaction equation

HRID 340985 reaction equation
[CH3:1][C:2]([OH:5])(C)[CH3:3].O.C([O-])([O-])=[O:8].[K+].[K+].[Si:13]([O:20][CH2:21][C@@H:22]([N:26]([CH3:39])[C:27]([NH:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:32]=1[Cl:38])=[O:28])CC=C)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]>CC(O)(C)C.O.C(OCC)(=O)C.CC[C@@H]1[C@@H]2C[C@H]([C@@H](OC3N=C(C4C=CC=CC=4)N=C(O[C@@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)C=3C3C=CC=CC=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1>[Si:13]([O:20][CH2:21][C@@H:22]([N:26]([CH3:39])[C:27]([NH:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:32]=1[Cl:38])=[O:28])[CH2:1][C@@H:2]([OH:5])[CH2:3][OH:8])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]

Participants

8

Reactant 4

HCID 962WaterHCID 6386tert-ButanolHCID 11430Potassium CarbonateHCID 57947454(S)-1-(1-(tert-butyldimethylsilyloxy)pent-4-en-2-yl)-3-(2-chloro-3-fluorobenzyl)-1-methylurea

Product 1

HCID 579478331-((2S,4R)-1-(tert-butyldimethylsilyloxy)-4,5-dihydroxypentan-2-yl)-3-(2-chloro-3-fluorobenzyl)-1-methylureaYield 55%

Reagents, catalysts & solvents 3

HCID 10306453(9S,9''S)-9,9''-((2,5-Diphenyl-4,6-pyrimidinediyl)bis(oxy))bis(10,11-dihydro-6'-methoxycinchonan)CatalystHCID 8857Ethyl AcetateSolventHCID 714019492-Methylpropan-2-ol--water (1/1)Solvent

Procedure

To a mixture of t-BuOH (300 mL) and water (300 mL) were added K2CO3 (17.0 g, 123 mmol,), (DHQD)2Pyr (361 mg, 0.41 mmol), K2OsO2(OH)4(151 mg, 0.41 mmol), K3FeCN6 (40.5 g, 123 mmol) at RT The mixture was stirred at RT for 2 h and then cooled to 0° C. To the mixture was added a suspension of (S)-1-(1-(tert-butyldimethylsilyloxy)pent-4-en-2-yl)-3-(2-chloro-3-fluorobenzyl)-1-methylurea (17.0 g, 41 mmol) in 100 mL of t-BuOH/water (1:1), and the reaction was stirred at 0° C. overnight. LC-MS indicted the reaction was completed, Na2S2O3.5H2O (30.6 g, 123 mmol) was added to the reaction, and the reaction was stirred at RT for 30 min. The mixture was diluted with ethyl acetate (1 L), washed with water (250 mL×2) and brine (250 mL), dried over Na2SO4, and filtered. The filtrate was concentrated and purified on silica gel to give 1-((2S,4R)-1-(tert-butyldimethylsilyloxy)-4,5-dihydroxypentan-2-yl)-3-(2-chloro-3-fluorobenzyl)-1-methylurea (10.1 g, 55%) as a colorless oil.

Workup

  1. temperaturecooled to 0° C
  2. additionTo the mixture was added
  3. stirringthe reaction was stirred at 0° C. overnight
  4. stirringthe reaction was stirred at RT for 30 min
  5. washwashed with water (250 mL×2) and brine (250 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. custompurified on silica gel

Sources & evidence

ORD record
ord-d2000da652504f98be6526808081379e
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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