Hydrochloric Acid → benzyl 5(S)-tert.-butoxycarbonylamino-6-cyclohexyl-4(S)-hydroxy-2(R)-methyl-1-hexyl ether

HRID 478046Notes

Reaction equation

HRID 478046 reaction equation
[CH2:1]([O:8][CH2:9][C@H:10]([CH3:13])[CH2:11]Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Mg].[C:15]([O:19][C:20]([NH:22][C@@H:23]([CH2:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[CH:24]=[O:25])=[O:21])([CH3:18])([CH3:17])[CH3:16].Cl>C(OCC)C>[C:15]([O:19][C:20]([NH:22][C@@H:23]([CH2:26][CH:27]1[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1)[C@@H:24]([OH:25])[CH2:11][C@@H:10]([CH3:13])[CH2:9][O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5462224MagnesiumHCID 7021514(S)-2-methyl-3-bromo-1-benzyloxypropaneHCID 10848617(S)-Tert-butyl 1-cyclohexyl-3-oxopropan-2-ylcarbamate

Product 1

HCID 22839050benzyl 5(S)-tert.-butoxycarbonylamino-6-cyclohexyl-4(S)-hydroxy-2(R)-methyl-1-hexyl ether

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

A Grignard solution prepared from 3.6 g of (S)-(+)-3-benzyloxy-2-methyl-propyl bromide (A. Fischli et al., Helv. Chim. Acta 60, 925 (1977)) and 360 mg of magnesium in diethyl ether is added dropwise within 15 minutes at 0° to 1.50 g of 2(S)-tert.-butoxycarbonylamino-3-cyclohexyl-propionaldehyde (J. Boger et al., J. Med. Chem. 28, 1779 (1985)) in 15 ml of diethyl ether After 30 minutes at 0°, the reaction solution is poured onto 50 ml of 1N HCl and the crude product (diastereoisomer ratio (4S):(4R)=4:1) is extracted with dichloromethane. The desired diastereoisomer having the 4(S)-configuration is isolated in pure form by flash chromatography on 250 g of silica gel 60 (eluant dichloromethane/ether 20:1). Rf (L)=0.10.

Workup

  1. extractionthe crude product (diastereoisomer ratio (4S):(4R)=4:1) is extracted with dichloromethane
  2. customis isolated in pure form by flash chromatography on 250 g of silica gel 60 (eluant dichloromethane/ether 20:1)

Sources & evidence

ORD record
ord-427b07429f3e48578e5e9c1bf320d850
Source dataset
uspto-grants-1989_12
Patent number
US04889869

Reaction notes

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