Acetic Acid → (9-(4-(2-(tert-Butyldimethylsilyloxy)ethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-methylthiazol-4-yl)methanone

HRID 470972Notes

Reaction equation

HRID 470972 reaction equation
FC(F)(F)C(O)=O.[CH3:8][C:9]1[S:10][CH:11]=[C:12]([C:14]([N:16]2[CH2:21][C:20]3([CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[O:19][CH2:18][CH2:17]2)=[O:15])[N:13]=1.[Si:27]([O:34][CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([CH2:43][CH:44]=O)=[CH:39][CH:38]=1)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN1C(=O)CCC1>[Si:27]([O:34][CH2:35][CH2:36][C:37]1[CH:38]=[CH:39][C:40]([CH2:43][CH2:44][N:24]2[CH2:25][CH2:26][C:20]3([O:19][CH2:18][CH2:17][N:16]([C:14]([C:12]4[N:13]=[C:9]([CH3:8])[S:10][CH:11]=4)=[O:15])[CH2:21]3)[CH2:22][CH2:23]2)=[CH:41][CH:42]=1)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 579893082-(4-(2-(tert-Butyldimethylsilyloxy)ethyl)phenyl)acetaldehydeHCID 66964121(2-Methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 57989178(9-(4-(2-(tert-Butyldimethylsilyloxy)ethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-methylthiazol-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

(2-Methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 4, step h) (0.26 g) was added to a solution of 2-(4-(2-(tert-butyldimethylsilyloxy)ethyl)phenyl)acetaldehyde (example 5, step c) (0.2 g) and acetic acid (0.04 mL) in NMP (5 mL). The resulting mixture was stirred for 5 min then sodium triacetoxyborohydride (0.23 g) was added. The mixture was stirred for 1 h, poured into pH 7.2 buffer (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic solutions were washed with pH 7.2 buffer (50 mL) and brine (50 mL), then dried over sodium sulphate, filtered and evaporated in vacuo. Purification was by silica gel chromatography eluting with 80:15:5 isohexane:ethyl acetate:triethylamine to 95:5 ethyl acetate:triethylamine to give the subtitled compound as a yellow oil. Yield 0.30 g.

Workup

  1. stirringThe mixture was stirred for 1 h
  2. additionpoured into pH 7.2 buffer (50 mL)
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined organic solutions were washed with pH 7.2 buffer (50 mL) and brine (50 mL)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customPurification
  9. washeluting with 80:15:5 isohexane

Sources & evidence

ORD record
ord-e1055e51fe4149ed8f423370db8fcaa6
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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