Hydrochloric Acid → t-Butyl N-(1-[2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl]-4-piperidyl)carbamate

HRID 258289Notes

Reaction equation

HRID 258289 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([CH:17]=O)([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1.[C:19]([O:23][C:24]([NH:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].Cl.C([BH3-])#N.[Na+].[OH-].[Na+]>CO.CCCCCC.CC(C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([CH2:17][N:30]4[CH2:29][CH2:28][CH:27]([NH:26][C:24](=[O:25])[O:23][C:19]([CH3:22])([CH3:20])[CH3:21])[CH2:32][CH2:31]4)([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 7238334-(N-Boc-amino)piperidineHCID 5003444Sodium cyanoborohydrideHCID 196986392-Chloro-9-formyl-9,10-dihydro-9,10-methanoanthracene

Product 1

HCID 19381052t-Butyl N-(1-[2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl]-4-piperidyl)carbamateYield 52%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolvent2×HCID 887MethanolSolventHCID 8058HexaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of 2-chloro-9-formyl-9,10-dihydro-9,10-methanoanthracene (3.64 g, 14.25 mmol, described in Example 107i), 4-t-butoxycarbonylaminopiperidine (3.57 g, 17.81 mmol), and activated 3A sieves (powderized, 3.64 g) in methanol (50 mL, sieve dried) was added methanolic hydrochloric acid (ca. 3.5 mL) until the pH was 7.50. After 2 h, the mixture was treated with sodium cyanoborohydride (895 mg, 14.25 mmol) in four portions over a 4 h period. After stirring the resulting mixture an additional 72 h, ethyl acetate (100 mL) and 3N sodium hydroxide (100 mL) and filtered through celite. The filtrate was treated with 3N sodium hydroxide (250 mL) and extracted with ethyl acetate (2×300 mL). The combined extracts was dried (sodium sulfate), filtered and concentrated to give a tan foam. Chromatography of this material over silica gel (eluting in sequence with 1) 90:10 acetone:hexane (6 L) and 2) 85:15 acetone:hexane (1 L)) to give the title compound as a white foam (3.24 g, 52%), mp 76.5°-80.0° C.; MS(CI): 439 (M+H); NMR (300 MHz,DMSO-d6): 1.37(m, 11H), 1.64(m, 2H), 2.21(m, 2H), 2.46(s, 2H), 2.92(m, 2H), 3.17-3.42(br m, part. submerged by H2O, 3H), 4.33(s, 1H), 6.72(m, 1H), 6.95(m, 3H), 7.19(m, 2H), 7.26(m, 2H).

Workup

  1. filtrationfiltered through celite
  2. additionThe filtrate was treated with 3N sodium hydroxide (250 mL)
  3. extractionextracted with ethyl acetate (2×300 mL)
  4. dry with materialThe combined extracts was dried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a tan foam

Sources & evidence

ORD record
ord-8460033a72544b77888ef1a8b89cb072
Source dataset
uspto-grants-1993_11
Patent number
US05266570

Reaction notes

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