2-{3-[(2-Azido-3-methyl-pentanoyl)-(3-methyl-butyryloxymethyl)-amino]-1-hydroxy-4-methyl-pentyl}-thiazole-4-carboxylic acid methyl ester → 2-{3-[(2-Azido-3-methyl-pentanoyl)-(3-methyl-butyryloxymethyl)-amino]-1-hydroxy-4-methyl-pentyl}-thiazole-4-carboxylic acid

HRID 446176Notes

Reaction equation

HRID 446176 reaction equation
[Sn](O)(C)(C)C.C[O:7][C:8]([C:10]1[N:11]=[C:12]([CH:15]([OH:40])[CH2:16][CH:17]([N:21]([C:30](=[O:39])[CH:31]([N:36]=[N+:37]=[N-:38])[CH:32]([CH3:35])[CH2:33][CH3:34])[CH2:22][O:23][C:24](=[O:29])[CH2:25][CH:26]([CH3:28])[CH3:27])[CH:18]([CH3:20])[CH3:19])[S:13][CH:14]=1)=[O:9]>ClC(Cl)C>[N:36]([CH:31]([CH:32]([CH3:35])[CH2:33][CH3:34])[C:30]([N:21]([CH2:22][O:23][C:24](=[O:29])[CH2:25][CH:26]([CH3:27])[CH3:28])[CH:17]([CH:18]([CH3:20])[CH3:19])[CH2:16][CH:15]([C:12]1[S:13][CH:14]=[C:10]([C:8]([OH:9])=[O:7])[N:11]=1)[OH:40])=[O:39])=[N+:37]=[N-:38]

Participants

4

Reactant 2

HCID 866503232-{3-[(2-Azido-3-methyl-pentanoyl)-(3-methyl-butyryloxymethyl)-amino]-1-hydroxy-4-methyl-pentyl}-thiazole-4-carboxylic acid methyl esterHCID 178477787HCID 178477787, compound

Product 1

HCID 866503222-{3-[(2-Azido-3-methyl-pentanoyl)-(3-methyl-butyryloxymethyl)-amino]-1-hydroxy-4-methyl-pentyl}-thiazole-4-carboxylic acidYield 36%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
55 °C

Procedure

Me3SnOH (736 mg, 4.07 mmol) was added to a 0.020 M solution of methyl ester 15 (260 mg, 0.509 mmol) in dichloroethane (25.0 mL). The reaction mixture was heated to 55° C. for 22 h and then concentrated. Normal-phase HPFC (100:0 to 90:10:1 CH2Cl2:MeOH:AcOH) followed by reverse-phase HPFC (20:80 to 100:0 MeCN:H2O) and lyophilization afforded 90.0 mg (36%) of 16 as an amorphous solid. [α]D23=+51.5 (c=1.0, MeOH). IR: 1088, 1217, 1651, 1735, 2100, 2964 cm−1. 1H NMR (500 MHz, MeOD): δ 0.88-0.94 (m, 9H), 0.97 (app t, 6H, J=6.8), 1.03 (d, 3H, J=6.5), 1.31 (sept, 1H, J=7.4), 1.72-1.81 (m, 1H), 1.82-1.90 (br s, 1H), 100-2.09 (m, 2H), 2.10-2.17 (m, 1H), 2.18-2.28 (m, 1H), 2.31 (app t, 2H, J=7.5), 3.75 (d, 1H, J=9.5), 4.44-4.68 (br s, 1H), 4.77 (d, 1H, J=9.5), 5.48 (d, 1H, J=12.5), 5.58 (d, 1H, J=12.5), 8.24 (s, 1H). 13C NMR (125 MHz, MeOD): δ 10.8, 16.0, 20.3, 20.6, 22.71, 22.73, 26.0, 26.5, 32.0, 36.7, 39.1, 44.1, 64.6, 69.5, 128.5, 149.2, 164.7, 173.58, 173.61, 179.5. HRMS (FAB) calcd for C22H35N5O6SNa (M+Na): 520.2206. Found: 520.2200.

Workup

  1. concentrationconcentrated

Sources & evidence

ORD record
ord-c16f9fc83ec547c4bd1949aaa9b63471
Source dataset
uspto-grants-2013_07
Patent number
US08476451B2

Reaction notes

Loading…