Ethanol → ethyl 2-((1R,3R)-3-(N-sulfinyl)amino-1-hydroxy-4-methylpentyl)thiazole-4-carboxylate

HRID 446183Notes

Reaction equation

HRID 446183 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C@H:11]([OH:24])[CH2:12][C:13](=[N:17][S@:18]([C:20]([CH3:23])([CH3:22])[CH3:21])=[O:19])[CH:14]([CH3:16])[CH3:15])[S:9][CH:10]=1)=[O:5])[CH3:2].[BH4-].[Na+].C1COCC1.CC(O)=O.CCO>C1COCC1.CCOC(C)=O.O>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C@H:11]([OH:24])[CH2:12][C@@H:13]([NH:17][S@:18]([C:20]([CH3:21])([CH3:22])[CH3:23])=[O:19])[CH:14]([CH3:15])[CH3:16])[S:9][CH:10]=1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 702EthanolHCID 4311764Sodium borohydrideHCID 23444217Acetic acid tetrahydrofuranHCID 86650324(+)-2-[(SS,1R)-1-Hydroxy-4-methyl-3-(2-methyl-propane-2-sulfinylimino)-pentyl]-thiazole-4-carboxylic acid ethyl ester

Product 1

HCID 24906124ethyl 2-((1R,3R)-3-(N-sulfinyl)amino-1-hydroxy-4-methylpentyl)thiazole-4-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of the product mixture containing β-hydroxy imine 31 (˜0.943 mmol) and imine 26 (˜0.178 mmol) in THF (3.50 mL) was cooled to −78° C. Ti(OEt)4 (0.469 mL, 2.24 mmol) was added, followed by NaBH4 (0.0847 g, 2.24 mmol), and the solution was stirred at −78° C. for 12 h. The solution was acidified using a 4:1 (v/v) solution of THF/AcOH (3.2 mL) followed by addition of EtOH (2 mL) and H2O (10 mL). The solution was warmed to rt and diluted with EtOAc. The mixture was washed once with brine, and the aqueous fraction was extracted once with EtOAc. The combined organic fractions were dried with Na2SO4, filtered, and concentrated. NMR analysis on the unpurified material established a 92:8 ratio of diastereomers. HPFC purification (100% EtOAc) produced 0.332 g (74%, over two steps) of the pure major diastereomer 32 as a colorless oil. [α]25D=+103.2 (c=1.0, CHCl3). IR (film): 1474, 1718, 2868, 2929, 2960, 3283 cm−1. 1H NMR (500 MHz, CDCl3): δ 0.90 (d, 3H, J=6.8 Hz), 0.93 (d, 3H, J=6.8 Hz), 1.29 (s, 9H), 1.40 (t, 3H, J=7.1 Hz), 1.70 (doublet of septets, 1H, J=2.3, 6.8 Hz), 1.91 (ddd, 1H, J=3.6, 11.5, 14.7 Hz), 2.30 (ddd, 1H, J=3.0, 11.8, 14.7 Hz), 3.30 (d, 1H, J=8.5 Hz), 3.40-3.47 (m, 1H), 4.38-4.45 (m, 2H), 5.18 (ddd, 1H, J=3.1, 6.7, 11.6 Hz), 5.48 (d, 1H, J=6.7 Hz), 8.11 (s, 1H). 13C NMR (125 MHz, CDCl3): δ 14.4, 17.3, 19.7, 23.0, 33.9, 40.6, 56.3, 58.5, 61.3, 67.8, 127.4, 147.0, 161.6, 177.6. HRMS (FAB) calcd. for C16H28N2O4NaS2 (M+Na): 399.1388. Found 399.1389.

Workup

  1. temperatureThe solution was warmed to rt
  2. washThe mixture was washed once with brine
  3. extractionthe aqueous fraction was extracted once with EtOAc
  4. dry with materialThe combined organic fractions were dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customHPFC purification (100% EtOAc)

Sources & evidence

ORD record
ord-d292a9937a6041e591b234eb56743bd1
Source dataset
uspto-grants-2013_07
Patent number
US08476451B2

Reaction notes

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