Trifluoroacetic acid → tert-butyl (3RS,4RS)-4-[4-(2-hydroxy-ethyl)-phenyl]-3-[4-(2-trimethylsilanyl-ethoxymethoxy)-naphthalen-2-ylmethoxy]-piperidine-1-carboxylate

HRID 1005113Notes

Reaction equation

HRID 1005113 reaction equation
[CH3:1][Si:2]([CH3:62])([CH3:61])[CH2:3][CH2:4][O:5][CH2:6][O:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([CH2:18][O:19][CH:20]2[CH:25]([C:26]3[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][O:34]C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)=[CH:28][CH:27]=3)[CH2:24][CH2:23][N:22]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:21]2)[CH:9]=1.FC(F)(F)C(O)=O.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(N(CC)CC)C>C(Cl)Cl.CO>[OH:34][CH2:33][CH2:32][C:29]1[CH:28]=[CH:27][C:26]([CH:25]2[CH2:24][CH2:23][N:22]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:21][CH:20]2[O:19][CH2:18][C:10]2[CH:9]=[C:8]([O:7][CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:1])([CH3:62])[CH3:61])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=2)=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 54268675tert-butyl (3RS,4RS)-3-[4-(2-trimethylsilanyl-ethoxymethoxy)-naphthalen-2-ylmethoxy]-4-[4-(2-trityloxy-ethyl)-phenyl]-piperidine-1-carboxylate

Product 1

HCID 86604449tert-butyl (3RS,4RS)-4-[4-(2-hydroxy-ethyl)-phenyl]-3-[4-(2-trimethylsilanyl-ethoxymethoxy)-naphthalen-2-ylmethoxy]-piperidine-1-carboxylateYield 98.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Selective cleavage of the trityl group was effected analogously to the procedure published by E. Krainer et al. in Tetrahedron Letters 1993, 1713-1716 by treating a solution of 780 mg (0.92 mmol) of tert-butyl (3RS,4RS)-3-[4-(2-trimethylsilanyl-ethoxymethoxy)-naphthalen-2-ylmethoxy]-4-[4-(2-trityloxy-ethyl)-phenyl]-piperidine-1-carboxylate in 15 ml of methylene chloride with a solution of 436 mg (3.68 mmol) of trifluoroacetic acid and 803 mg (3.68 mmol) of trifluoroacetic anhydride in 2 ml of methylene chloride. After 30 seconds the reaction mixture was cooled to 0° C. and treated with 4 ml of triethylamine. After 5 minutes 10 ml of methanol were added and the mixture was stirred for 10 minutes. Subsequently, the mixture was washed with saturated sodium hydrogen carbonate solution and the aqueous phase was thereafter back-extracted with 10 ml of methylene chloride. The combined organic phases were dried over sodium sulphate and then evaporated under reduced pressure. The crude product was chromatographed on silica gel using a 4:1 mixture of hexane and ethyl acetate as the eluent. There were obtained 553 mg of tert-butyl (3RS,4RS)-4-[4-(2-hydroxy-ethyl)-phenyl]-3-[4-(2-trimethylsilanyl-ethoxy-methoxy)-naphthalen-2-ylmethoxy]-piperidine-1-carboxylate as a colourless oil.

Workup

  1. washSubsequently, the mixture was washed with saturated sodium hydrogen carbonate solution
  2. extractionthe aqueous phase was thereafter back-extracted with 10 ml of methylene chloride
  3. dry with materialThe combined organic phases were dried over sodium sulphate
  4. customevaporated under reduced pressure
  5. customThe crude product was chromatographed on silica gel using
  6. additiona 4:1 mixture of hexane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-98ce26cc8e284a5c90840cfb133b6cb9
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

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