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

HRID 507883Notes

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.[BH4-].[K+].N[C@H:23]([CH2:36]O)[C@@H:24](C1C=CC(S(C)(=O)=O)=CC=1)O.C(N(CC)CC)C>CO.CC(C)=O.C1(C)C=CC=CC=1>[CH3:24][C:23]1([CH3:36])[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

Conditions

Temperature: 75 °C

Procedure

(2S,3R)-Ethyl-2-amino-3-[4-(methylsulfonyl)phenyl]-3-hydroxy-propanoate (Compound IV) (100 g, 0.3480 moles) in methanol (450 mL) reacts with potassium borohydride (28.2 g, 0.5220 moles) over 4-8 hours at 50-60° C. to quantitatively yield (1R,2R)-2-amino-1-[4-(methylsulfonyl)phenyl]-1,3-propandiol (Compound VII: R1 is methylsulfonyl) (85.4 g, 0.3480 moles) in solution. Toluene (450 mL) and acetone (450 mL) replace methanol which distills off. Addition of triethylamine (8.8 g, 0.0870 moles) with heating at 70-80° C. for 12-18 hours yields (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 (44.5 g, 0.4402 moles) and acetyl chloride (30.0 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 (200 mL) then drying yields (4R,5R)-3-acetyl-2,2-dimethyl-4-hydroxymethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine (Compound II).

Workup

distillationdistills off

Sources & evidence

ORD record: ord-07ccd33db7834c0cb54a749a8bdfe528
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07786329B2

Reaction notes

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