Sodium Bicarbonate → (9-((5-(2-(Tert-butyldimethylsilyloxy)ethyl)thiophen-3-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 471306Notes

Reaction equation

HRID 471306 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][C:11]1[S:15][CH:14]=[C:13]([CH:16]=O)[CH:12]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.[CH:25]([C:28]1[S:29][CH:30]=[C:31]([C:33]([N:35]2[CH2:40][C:39]3([CH2:45][CH2:44][NH:43][CH2:42][CH2:41]3)[O:38][CH2:37][CH2:36]2)=[O:34])[N:32]=1)([CH3:27])[CH3:26].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>CN1CCCC1=O.C(O)(=O)C.O>[Si:1]([O:8][CH2:9][CH2:10][C:11]1[S:15][CH:14]=[C:13]([CH2:16][N:43]2[CH2:44][CH2:45][C:39]3([O:38][CH2:37][CH2:36][N:35]([C:33]([C:31]4[N:32]=[C:28]([CH:25]([CH3:26])[CH3:27])[S:29][CH:30]=4)=[O:34])[CH2:40]3)[CH2:41][CH2:42]2)[CH:12]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 579889035-(2-(Tert-butyldimethylsilyloxy)ethyl)thiophene-3-carbaldehydeHCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 57988978(9-((5-(2-(Tert-butyldimethylsilyloxy)ethyl)thiophen-3-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

5-(2-(tert-butyldimethylsilyloxy)ethyl)thiophene-3-carbaldehyde (0.6 g) (example 278, step c) was added to (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (0.94 g) (example 22, step b) in a mixture of N-methyl-2-pyrrolidinone (5 mL) and acetic acid (0.13 mL) and stirred for 30 min. Sodium triacetoxyborohydride (0.71 g) was then added and the mixture stirred overnight. The reaction was poured into water (100 mL), the pH was adjusted to 8 using saturated sodium bicarbonate solution and the resulting aqueous solution extracted with ethyl acetate (3×100 mL). The combined organic solutions were washed with water (3×100 mL), brine (100 mL), dried over sodium sulphate, filtered and evaporated. The residue was purified by silica gel chromatography eluting with 77.5:17.5:5 i-hexane:ethyl acetate:triethylamine to 47.5:47.5:5 i-hexane:ethyl acetate:triethylamine gradient. The fractions containing product were combined and evaporated in vacuo to give the subtitled compound as a clear oil. Yield 0.8 g.

Workup

  1. stirringthe mixture stirred overnight
  2. extractionthe resulting aqueous solution extracted with ethyl acetate (3×100 mL)
  3. washThe combined organic solutions were washed with water (3×100 mL), brine (100 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 77.5:17.5:5 i-hexane
  9. additionThe fractions containing product
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-1cb927f1056c46559a4f2c987c810146
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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