Lithium Chloride → benzyl N-[(4R)-4-(3-tert-butylthioureido)-5-hydroxypentyl]carbamate

HRID 47772Notes

Reaction equation

HRID 47772 reaction equation
[Cl-].[Li+].[CH2:3]([O:10][C:11]([NH:13][CH2:14][CH2:15][CH2:16][C@@H:17]([NH:23][C:24]([NH:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[S:25])[C:18](OCC)=[O:19])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[BH4-].[Na+]>C(O)C.O1CCCC1>[C:27]([NH:26][C:24](=[S:25])[NH:23][C@@H:17]([CH2:18][OH:19])[CH2:16][CH2:15][CH2:14][NH:13][C:11](=[O:12])[O:10][CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)([CH3:30])([CH3:28])[CH3:29]

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 4311764Sodium borohydride2×HCID 86584443ethyl (2R)-5-{[(benzyloxy)carbonyl]amino}-2-(3-tert-butylthioureido)pentanoate

Product 1

HCID 86584442benzyl N-[(4R)-4-(3-tert-butylthioureido)-5-hydroxypentyl]carbamateYield 66.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

2.24 g of lithium chloride are added with stirring to a solution of 16 g of ethyl (2R)-5-{[(benzyloxy)carbonyl]amino}-2-(3-tert-butyl-thioureido)pentanoate in 200 cm3 of ethanol and 100 cm3 of tetrahydrofuran. After stirring for 15 minutes at a temperature in the region of 0° C., 2.24 g of sodium borohydride are added. After stirring for 20 hours at a temperature in the region of 20° C., a further 0.5 g of sodium borohydride is added. The reaction medium is filtered and the filtrates are concentrated under reduced pressure (1 kPa) at a temperature in the region of 40° C. The residue is chromatographed at atmospheric pressure on a column of silica gel (particle size 60-200μ; diameter 5.6 cm; height 40 cm), eluting with a mixture of dichloromethane/ethyl acetate (8/2 by volume) and a mixture of dichloromethane/ethyl acetate (6/4 by volume). The fractions containing the expected product are combined and then concentrated under the above conditions. 9.6 g of benzyl N-[(4R)-4-(3-tert-butylthioureido)-5-hydroxypentyl]carbamate are obtained in the form of a yellow oil [1H NMR spectrum (300 MHz, (CD3)2SO-d6, δ in ppm): from 1.30 to 1.60 (mt: 4H); 1.42 (s: 9H); 3.00 (mt: 2H); from 3.25 to 3.40 (mt: 1H); 3.45 (mt: 1H); 4.21 (unresolved complex: 1H); 4.76 (unresolved complex: 1H); 5.02 (s: 2H); 7.09 (d, J=8.5 Hz: 1H); 7.17 (broad s: 1H); 7.27 (t, J 5.5 Hz: 1H); from 7.30 to 7.45 (mt: 5H)].

Workup

  1. additionare added
  2. filtrationThe reaction medium is filtered
  3. concentrationthe filtrates are concentrated under reduced pressure (1 kPa) at a temperature in the region of 40° C
  4. customThe residue is chromatographed at atmospheric pressure on a column of silica gel (particle size 60-200μ; diameter 5.6 cm; height 40 cm)
  5. washeluting with a mixture of dichloromethane/ethyl acetate (8/2 by volume)
  6. additiona mixture of dichloromethane/ethyl acetate (6/4 by volume)
  7. additionThe fractions containing the expected product
  8. concentrationconcentrated under the above conditions

Sources & evidence

ORD record
ord-10264d529204426280935152973422cf
Source dataset
uspto-grants-2004_03
Patent number
US06699895B2

Reaction notes

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