tert-Butyl bromoacetate → tert-butyl (1S,2S)-(6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl)acetate

HRID 2394992Notes

Reaction equation

HRID 2394992 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([CH:12]([CH3:14])[CH3:13])[C@:7]([CH2:16][CH2:17][O:18]S(C1C=CC(C)=CC=1)(=O)=O)([OH:15])[CH2:6][CH2:5]2.FC1C=C2C(=CC=1)[C@H](C(C)C)C(=O)CC2.BrCC([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=O.[Mg]>>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([CH:12]([CH3:14])[CH3:13])[C@:7]([CH2:16][C:17]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:18])([OH:15])[CH2:6][CH2:5]2

Participants

5

Reactant 4

HCID 79177tert-Butyl bromoacetateHCID 5462224MagnesiumHCID 10987431(S)-6-Fluoro-1-isopropyl-3,4-dihydronaphthalen-2(1H)-oneHCID 86657121(1S,2S)-6-fluoro-1-isopropyl-2-[2-(4-toluenesulfonyloxy)ethyl]-1,2,3,4-tetrahydronaphthalene-2-ol

Product 1

HCID 57135574tert-butyl (1S,2S)-(6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl)acetate

Procedure

The (1S,2S)-6-fluoro-1-isopropyl-2-[2-(4-toluenesulfonyloxy) ethyl]-1,2,3,4-tetrahydro-naphthalene-2-ol, as described in U.S. Pat. No. 4,680,310 (also to Hoffmann-La Roche), is prepared by reacting (S)-6-fluoro-1-isopropyl-3,4-dihydro-1H-naphthalen-2-one with tert-butyl bromoacetate in the presence of activated magnesium to form tert-butyl (1S, 2S)-(6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetate, which is reduced with lithium aluminum hydride to form (1S,2S)-6-fluoro-2-(2-hydroxyethyl)-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-ol, and then reacted with 4-toluenesulfonyl chloride in pyridine to form the (1S,2S)-6-fluoro-1-isopropyl-2-[2-(4-toluenesulfonyloxy) ethyl]-1,2,3,4-tetrahydronaphthalene-2-ol.

Workup

  1. custom4,680,310 (also to Hoffmann-La Roche), is prepared

Sources & evidence

ORD record
ord-5b4fd427df2d4c20844009b17ac01c8f
Source dataset
uspto-grants-1998_09
Patent number
US05811556

Reaction notes

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