Sodium triacetoxyborohydride → 1-(9-((4-(2-(tert-Butyldimethylsilyloxy)ethyl)thiophen-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)-2,2,2-trifluoroethanone

HRID 1689300Notes

Reaction equation

HRID 1689300 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]([F:24])([F:23])[C:10]([N:12]1[CH2:17][C:16]2([CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[O:15][CH2:14][CH2:13]1)=[O:11].[Si:25]([O:32][CH2:33][CH2:34][C:35]1[CH:36]=[C:37]([CH:40]=O)[S:38][CH:39]=1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].[Si](OCCC1C=CSC=1C=O)(C(C)(C)C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN1CCCC1=O.O.CC(O)=O>[Si:25]([O:32][CH2:33][CH2:34][C:35]1[CH:36]=[C:37]([CH2:40][N:20]2[CH2:21][CH2:22][C:16]3([O:15][CH2:14][CH2:13][N:12]([C:10](=[O:11])[C:9]([F:8])([F:23])[F:24])[CH2:17]3)[CH2:18][CH2:19]2)[S:38][CH:39]=1)([C:28]([CH3:29])([CH3:31])[CH3:30])([CH3:27])[CH3:26]

Participants

8

Reactant 4

HCID 5049666Sodium triacetoxyborohydrideHCID 579889073-(2-(Tert-butyldimethylsilyloxy)ethyl)thiophene-2-carbaldehydeHCID 579891104-(2-(Tert-butyldimethylsilyloxy)ethyl)thiophene-2-carbaldehydeHCID 866367502,2,2-Trifluoro-1-(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone trifluoroacetate

Product 1

HCID 579892241-(9-((4-(2-(tert-Butyldimethylsilyloxy)ethyl)thiophen-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)-2,2,2-trifluoroethanone

Reagents, catalysts & solvents 3

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

Procedure

2,2,2-Trifluoro-1-(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone trifluoroacetate (example 12, step d) (1.084 g) was added to a stirred solution of a 4:1 mixture of 4-(2-(tert-butyldimethylsilyloxy)ethyl)thiophene-2-carbaldehyde and 3-(2-(tert-butyldimethylsilyloxy)ethyl)thiophene-2-carbaldehyde (example 27, step b) (1.0 g), and AcOH (0.16 mL) in N-methyl-2-pyrrolidinone (15 mL). After 5 min, sodium triacetoxyborohydride (1.57 g) was added. After 16 h water was added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed three times with water and evaporated in vacuo. Purification by silica gel chromatography eluting with ethyl acetate:isohexane:triethylamine, 1:20:1 separated the two isomeric products and gave the subtitled compound as an oil. Yield 1.04 g.

Workup

  1. extractionthe mixture extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed three times with water
  3. customevaporated in vacuo
  4. customPurification by silica gel chromatography
  5. washeluting with ethyl acetate
  6. customisohexane:triethylamine, 1:20:1 separated the two isomeric products

Sources & evidence

ORD record
ord-1fadb069705346a7bdd95b48f50c66be
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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