2-Methoxypropene → (4R,5R)-2,2-dimethyl-4-hydroxymethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine

HRID 507884Notes

Reaction equation

HRID 507884 reaction equation
C(O[C:4](=[O:19])[C@@H:5]([NH2:18])[C@@H:6]([C:8]1[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=1)[OH:7])C.[H-].[Al+3].[Li+].[H-].[H-].[H-].N[C@H:27]([CH2:40]O)[C@@H:28](C1C=CC(S(C)(=O)=O)=CC=1)O.COC(C)=C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1.C1(C)C(C)=CC=CC=1.C(OCC)(=O)C>[CH3:28][C:27]1([CH3:40])[NH:18][C@H:5]([CH2:4][OH:19])[C@@H:6]([C:8]2[CH:9]=[CH:10][C:11]([S:14]([CH3:17])(=[O:15])=[O:16])=[CH:12][CH:13]=2)[O:7]1

Participants

9

Reactant 5

HCID 83002-MethoxypropeneHCID 521998p-Toluenesulfonic acid monohydrateHCID 6452441(R(R*,R*))-2-Amino-1-(p-(methylsulphonyl)phenyl)propane-1,3-diol2×HCID 21226445Aluminium lithium hydrideHCID 34175685(2S,3R)-Ethyl-2-amino-3-[4-(methylsulfonyl)phenyl]-3-hydroxy-propanoate2×

Product 1

HCID 68470177(4R,5R)-2,2-dimethyl-4-hydroxymethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine

Reagents, catalysts & solvents 3

HCID 7237O-XyleneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2S,3R)-Ethyl-2-amino-3-[4-(methylsulfonyl)phenyl]-3-hydroxy-propanoate (Compound IV) (100 g, 0.3480 moles) in tetrahydrofuran (500 mL) reacts with lithium aluminum hydride (16.0 g, 0.4224 moles) over 4-8 hours at 60-70° C. to quantitatively yield (1R,2R)-2-amino-1-[4-methylsulfonyl)phenyl]-1,3-propandiol (Compound VII: R1 is methylsulfonyl) (85.36 g, 0.3480 moles). Addition of ethyl acetate (75 mL) destroys any excess lithium aluminum hydride. Addition of xylene (600 mL), 2-methoxypropene (37.6 g, 0.5220 moles), and p-toluenesulfonic acid monohydrate (6.6 g, 0.0348 moles) with agitation at 20-30° C. for 10-16 hours produces (4R,5R)-2,2-dimethyl-4-hydroxymethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine (Compound VIII: R1 is methylsulfonyl and R2 and R3 are methyl). Addition of triethylamine (81.3 g, 0.8039 moles) and acetyl chloride (30.0 g, 0.3828 moles) at 20-25° C. for 2-4 hours then addition of water (650 mL) precipitates the crude product. Filtration, washing with water (300 mL) then drying yields (4R,5R)-3-acetyl-2,2-dimethyl-4-hydroxymethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine (Compound II).

Workup

  1. customdestroys any excess lithium aluminum hydride

Sources & evidence

ORD record
ord-2ecd1f40b2c24c1fa9b26e1d3fb3fe39
Source dataset
uspto-grants-2010_08
Patent number
US07786329B2

Reaction notes

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