Triethylamine → (R)-tert-Butyl 2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl(4-(2-(4-(2,2,2-trifluoroacetyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethoxy)benzyl)carbamate

HRID 471273Notes

Reaction equation

HRID 471273 reaction equation
CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][N:16]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:17][C@H:18]([OH:30])[C:19]2[C:27]3[S:26][C:25](=[O:28])[NH:24][C:23]=3[C:22]([OH:29])=[CH:21][CH:20]=2)=[CH:11][CH:10]=1)(=O)=O.FC(F)(F)C(O)=O.[F:45][C:46]([F:61])([F:60])[C:47]([N:49]1[CH2:54][C:53]2([CH2:59][CH2:58][NH:57][CH2:56][CH2:55]2)[O:52][CH2:51][CH2:50]1)=[O:48].C(N(CC)CC)C>CC#N>[OH:30][C@H:18]([C:19]1[C:27]2[S:26][C:25](=[O:28])[NH:24][C:23]=2[C:22]([OH:29])=[CH:21][CH:20]=1)[CH2:17][N:16]([CH2:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:7][CH2:6][N:57]2[CH2:58][CH2:59][C:53]3([O:52][CH2:51][CH2:50][N:49]([C:47](=[O:48])[C:46]([F:45])([F:60])[F:61])[CH2:54]3)[CH2:55][CH2:56]2)=[CH:14][CH:13]=1)[C:31](=[O:32])[O:33][C:34]([CH3:37])([CH3:35])[CH3:36]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 57989363(R)-2-(4-((tert-butoxycarbonyl(2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl)amino)methyl)phenoxy)ethyl methanesulfonateHCID 866367502,2,2-Trifluoro-1-(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone trifluoroacetate

Product 1

HCID 57989007(R)-tert-Butyl 2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl(4-(2-(4-(2,2,2-trifluoroacetyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethoxy)benzyl)carbamate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of (R)-2-(4-((tert-butoxycarbonyl(2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl)amino)methyl)phenoxy)ethyl methanesulfonate (example 108, step c) (2.20 g) in MeCN (8.5 mL) was added dropwise to a solution of 2,2,2-trifluoro-1-(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone trifluoroacetate (example 12, step d) (1.18 g) and triethylamine (0.81 mL) in MeCN (8.5 mL) at RT under argon. The resulting mixture was stirred at 60° C. under argon for 25 h. After cooling to RT the solvent was removed in vacuo. The brown residue was taken up in DCM (35 mL), washed with water (2×35 mL), dried over sodium sulphate, filtered and evaporated in vacuo. The yellow solid was purified by silica gel chromatography eluting with 0-10% MeOH/DCM to give the subtitle compound as a yellow solid. Yield 729 mg.

Workup

  1. temperatureAfter cooling to RT the solvent
  2. customwas removed in vacuo
  3. washwashed with water (2×35 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe yellow solid was purified by silica gel chromatography
  8. washeluting with 0-10% MeOH/DCM

Sources & evidence

ORD record
ord-53b45ff7656045a3b83f5c446cb47d55
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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