tert-Butyldimethylsilyl chloride → tert-Butyl 2-(3-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)phenethoxy)-N-cyclohexylpropanamido)ethyl(2-(5-(tert-butyldimethylsilyloxy)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)carbamate

HRID 446478Notes

Reaction equation

HRID 446478 reaction equation
[O:1]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][C:13]3[CH:14]=[C:15]([CH:54]=[CH:55][CH:56]=3)[CH2:16][CH2:17][O:18][CH2:19][CH2:20][C:21]([N:23]([CH2:30][CH2:31][N:32]([CH2:40][CH2:41][C:42]3[C:47]4[O:48][CH2:49][C:50](=[O:52])[NH:51][C:46]=4[C:45]([OH:53])=[CH:44][CH:43]=3)[C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)=[O:22])[CH2:8][CH2:7]2)[CH2:5][NH:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[Si:66](Cl)([C:69]([CH3:72])([CH3:71])[CH3:70])([CH3:68])[CH3:67].C(=O)(O)[O-].[Na+]>CN1C(=O)CCC1>[O:1]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][C:13]3[CH:14]=[C:15]([CH:54]=[CH:55][CH:56]=3)[CH2:16][CH2:17][O:18][CH2:19][CH2:20][C:21]([N:23]([CH2:30][CH2:31][N:32]([CH2:40][CH2:41][C:42]3[C:47]4[O:48][CH2:49][C:50](=[O:52])[NH:51][C:46]=4[C:45]([O:53][Si:66]([C:69]([CH3:72])([CH3:71])[CH3:70])([CH3:68])[CH3:67])=[CH:44][CH:43]=3)[C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:36])[CH3:37])[CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)=[O:22])[CH2:8][CH2:7]2)[CH2:5][NH:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 28928tert-Butyldimethylsilyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 58168531tert-Butyl 2-(3-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)phenethoxy)-N-cyclohexylpropanamido)ethyl(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)carbamate

Product 1

HCID 58168569tert-Butyl 2-(3-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)phenethoxy)-N-cyclohexylpropanamido)ethyl(2-(5-(tert-butyldimethylsilyloxy)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)carbamate

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

tert-Butyl 2-(3-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)phenethoxy)-N-cyclohexylpropanamido)ethyl(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)carbamate [Examples 81-175, step h] (0.97 g) was dissolved in NMP (10 mL) and treated with Hunig's base (1.0 mL) followed by tert-butyldimethylsilyl chloride (0.45 g). The resulting mixture was stirred at room temperature for 3 hours. The solution was poured into saturated sodium bicarbonate solution and extracted three times with ethyl acetate. The combined extracts were washed three times with water, once with brine, then dried (MgSO4) and concentrated onto flash silica (20 mL) in-vacuo. The resulting powder was purified by flash chromatography on silica eluted with triethylamine:methanol:dichloromethane (1:5:94) to afford the subtitled compound as a white foam. Yield 0.81 g.

Workup

  1. extractionextracted three times with ethyl acetate
  2. washThe combined extracts were washed three times with water
  3. dry with materialonce with brine, then dried (MgSO4)
  4. concentrationconcentrated onto flash silica (20 mL) in-vacuo
  5. customThe resulting powder was purified by flash chromatography on silica
  6. washeluted with triethylamine:methanol:dichloromethane (1:5:94)

Sources & evidence

ORD record
ord-fe22f680bdc349d3bc1c82f7d52d9413
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

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