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

HRID 507890Notes

Reaction equation

[BH4-].[K+].[CH3:3][C:4]1([CH3:21])[NH:8][C@H:7]([CH2:9][OH:10])[C@@H:6]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[O:5]1.C(=O)([O-])[O-].[K+].[K+].[Cl:28][CH:29]([Cl:33])[C:30](Cl)=[O:31]>O>[Cl:28][CH:29]([Cl:33])[C:30]([N:8]1[C@H:7]([CH2:9][OH:10])[C@@H:6]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:18])=[O:19])=[CH:13][CH:12]=2)[O:5][C:4]1([CH3:21])[CH3:3])=[O:31]

Participants

Conditions

Temperature: 55 °C

Procedure

(2S,3R)-Ethyl-2-amino-3-[4-(methylsulfonyl)phenyl]-3-hydroxy-propanoate (Compound IV) (100 g, 0.3480 moles) in 500 mL of methanol reacts with 2,2-dimethoxypropane (39.9 g, 0.3828 moles) and lithium carbonate at 60-70° C. to yield (4S,5R)-2,2-dimethyl-4-ethylcarboxyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine (Compound XIVa) (113.9 g, 0.3480 moles). Addition of potassium borohydride (28.2 g, 0.5220 moles) with stirring over 4-8 hours at 50-60° C. then yields (4R,5R)-2,2-dimethyl-4-hydroxymethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine (Compound VIIIa). Addition of potassium carbonate (19.0 g, 0.1914 moles) and dichloroacetyl chloride (56.4 g, 0.3828 moles) at 20-25° C. for 2-4 hours then addition of water (500 mL) precipitates the crude product. Filtration, washing with water (250 mL) then drying yields (4R,5R)-3-dichloroacetyl-2,2-dimethyl-4-hydroxymethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine (Compound XIIa).

Workup

customprecipitates the crude product
filtrationFiltration
washwashing with water (250 mL)
customthen drying

Sources & evidence

ORD record: ord-5fca592befb147c3923e7f27c22317d7
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07786329B2

Reaction notes

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