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

HRID 416419Notes

Reaction equation

HRID 416419 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-4e6b1377b1ae4c3a97b871e1aecd6d6f
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

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